Gene Summary

Gene:ERCC2; ERCC excision repair 2, TFIIH core complex helicase subunit
Aliases: EM9, TTD, XPD, TTD1, COFS2, TFIIH
Summary:The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:general transcription and DNA repair factor IIH helicase subunit XPD
Source:NCBIAccessed: 30 August, 2019


What does this gene/protein do?
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Pathways:What pathways are this gene/protein implicaed in?
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Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 30 August 2019 using data from PubMed using criteria.

Literature Analysis

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Tag cloud generated 30 August, 2019 using data from PubMed, MeSH and CancerIndex

Latest Publications: ERCC2 (cancer-related)

Rudnicka K, Backert S, Chmiela M
Genetic Polymorphisms in Inflammatory and Other Regulators in Gastric Cancer: Risks and Clinical Consequences.
Curr Top Microbiol Immunol. 2019; 421:53-76 [PubMed] Related Publications
Helicobacter pylori infection is associated with the development of a chronic inflammatory response, which may induce peptic ulcers, gastric cancer (GC), and mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic H. pylori infection promotes the genetic instability of gastric epithelial cells and interferes with the DNA repair systems in host cells. Colonization of the stomach with H. pylori is an important cause of non-cardia GC and gastric MALT lymphoma. The reduction of GC development in patients who underwent anti-H. pylori eradication schemes has also been well described. Individual susceptibility to GC development depends on the host's genetic predisposition, H. pylori virulence factors, environmental conditions, and geographical determinants. Biological determinants are urgently sought to predict the clinical course of infection in individuals with confirmed H. pylori infection. Possible candidates for such biomarkers include genetic aberrations such as single-nucleotide polymorphisms (SNPs) found in various cytokines/growth factors (e.g., IL-1β, IL-2, IL-6, IL-8, IL-10, IL-13, IL-17A/B, IFN-γ, TNF, TGF-β) and their receptors (IL-RN, TGFR), innate immunity receptors (TLR2, TLR4, CD14, NOD1, NOD2), enzymes involved in signal transduction cascades (PLCE1, PKLR, PRKAA1) as well as glycoproteins (MUC1, PSCA), and DNA repair enzymes (ERCC2, XRCC1, XRCC3). Bacterial determinants related to GC development include infection with CagA-positive (particularly with a high number of EPIYA-C phosphorylation motifs) and VacA-positive isolates (in particular s1/m1 allele strains). The combined genotyping of bacterial and host determinants suggests that the accumulation of polymorphisms favoring host and bacterial features increases the risk for precancerous and cancerous lesions in patients.

Sandoz J, Nagy Z, Catez P, et al.
Functional interplay between TFIIH and KAT2A regulates higher-order chromatin structure and class II gene expression.
Nat Commun. 2019; 10(1):1288 [PubMed] Free Access to Full Article Related Publications
The TFIIH subunit XPB is involved in combined Xeroderma Pigmentosum and Cockayne syndrome (XP-B/CS). Our analyses reveal that XPB interacts functionally with KAT2A, a histone acetyltransferase (HAT) that belongs to the hSAGA and hATAC complexes. XPB interacts with KAT2A-containing complexes on chromatin and an XP-B/CS mutation specifically elicits KAT2A-mediated large-scale chromatin decondensation. In XP-B/CS cells, the abnormal recruitment of TFIIH and KAT2A to chromatin causes inappropriate acetylation of histone H3K9, leading to aberrant formation of transcription initiation complexes on the promoters of several hundred genes and their subsequent overexpression. Significantly, this cascade of events is similarly sensitive to KAT2A HAT inhibition or to the rescue with wild-type XPB. In agreement, the XP-B/CS mutation increases KAT2A HAT activity in vitro. Our results unveil a tight connection between TFIIH and KAT2A that controls higher-order chromatin structure and gene expression and provide new insights into transcriptional misregulation in a cancer-prone DNA repair-deficient disorder.

Wang L, Wang LL, Shang D, et al.
Gene polymorphism of DNA repair gene X-ray repair cross complementing group 1 and xeroderma pigmentosum group D and environment interaction in non-small-cell lung cancer for Chinese nonsmoking female patients.
Kaohsiung J Med Sci. 2019; 35(1):39-48 [PubMed] Related Publications
An association between genetic polymorphisms in encoding X-ray repair cross complementing group 1 (XRCC1) and encoding xeroderma pigmentosum group D (XPD) and risks of non-small-cell lung cancer (NSCLC) in East Chinese Han population has been observed. Herein we hypothesized that genetic polymorphisms in these two DNA repair genes are likely to be important in the NSCLC in Chinese nonsmoking female patients. We recruited 327 nonsmoking female patients with NSCLC and 342 individuals with benign lung diseases or healthy controls. Genotype frequencies of XRCC1 T-77C, Arg194Trp, Arg280His and Arg399Gln, Pro206Pro, and XPD Asp312Asn and Lys751Gln were calculated after Polymerase Chain Reaction amplification and sequencing. Generalized multifactor dimensionality reduction (GMDR) was used to detect the interactive effect of XRCC1 and XPD gene polymorphisms. The ratio of cooking oil mist exposure history and soot exposure history, and the gene frequencies of XRCC1 T-77C TC + CC, XRCC1 AG + GG, XRCC1 399Gln/Gln, and XPD 751Gln/Gln were higher in female patients with NSCLC than those with benign lung diseases or healthy controls. The haplotypes of XRCC1 T-Arg-Arg-Gln and XRCC1 C-Arg-Arg-Arg were positively associated with the NSCLC occurrence in nonsmoking female patients. GMDR discovered that there was an interactive model of XRCC1 and XPD genes in multiple gene loci. Logistic regression analysis showed that XRCC1 T-77C, XRCC1 Pro206Pro polymorphism, cooking oil mist and soot exposure history and tumor-node-metastasis (TNM) stage were related to NSCLC occurrence for nonsmoking female patients. Taken together, XRCC1 and XPD polymorphisms, cooking oil mist, and soot exposure history may be interactively correlated with NSCLC incidence for nonsmoking female patients.

Tse J, Ghandour R, Singla N, Lotan Y
Molecular Predictors of Complete Response Following Neoadjuvant Chemotherapy in Urothelial Carcinoma of the Bladder and Upper Tracts.
Int J Mol Sci. 2019; 20(4) [PubMed] Free Access to Full Article Related Publications
Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) is often regarded as one entity and is managed generally with similar principles. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is an established standard of care in UCB, strong evidence for a similar approach is lacking in UTUC. The longest survival is seen in patients with complete response (pT0) on pathological examination of the RC specimen, but impact of delayed RC in nonresponders may be detrimental. The rate of pT0 following NAC in UTUC is considerably lower than that in UCB due to differences in access and instrumentation. Molecular markers have been evaluated to try to predict response to chemotherapy to reduce unnecessary treatment and expedite different treatment for nonresponders. A variety of potential biomarkers have been evaluated to predict response to cisplatin based chemotherapy including DNA repair genes (

Lim YC, Kim H, Lim SM, Kim JS
Genetic analysis of a novel antioxidant multi-target iron chelator, M30 protecting against chemotherapy-induced alopecia in mice.
BMC Cancer. 2019; 19(1):149 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Chemotherapy-induced alopecia has been well documented as a cause of distress to patients undergoing cancer treatment. Almost all traditional chemotherapeutic agents cause severe alopecia. Despite advances in the treatment of chemotherapy-induced alopecia, there is no effective treatment for preventing chemotherapy-induced alopecia.
METHODS: In the present study, we investigated the potential role of a multi-target iron chelator, M30 in protecting against cyclophosphamide-induced alopecia in C57BL/6 mice implanted with an osmotic pump. M30 enhanced hair growth and prevented cyclophosphamide-induced abnormal hair in the mice. Furthermore, we examined the gene expression profiles derived from skin biopsy specimens of normal mice, cyclophosphamide-treated mice, and cyclophosphamide treated mice with M30 supplement.
RESULTS: The top genes namely Tnfrsf19, Ercc2, Lama5, Ctsl, and Per1 were identified by microarray analysis. These genes were found to be involved in the biological processes of hair cycle, hair cycle phase, hair cycle process, hair follicle development, hair follicle maturation, hair follicle morphogenesis, regulation of hair cycle.
CONCLUSION: Our study demonstrates that M30 treatment is a promising therapy for cyclophosphamide-induced alopecia and suggests that the top five genes have unique preventive effects in cyclophosphamide-induced transformation.

Avci H, Iplik ES, Aydemir L, et al.
Are XPD and XPG gene variants related to the mechanism of oral squamous cell carcinoma?
Cell Mol Biol (Noisy-le-grand). 2018; 64(15):94-99 [PubMed] Related Publications
Oral cavity cancers have anatomically a big part of the body system and include several types of cancer. The aim of the study is to investigate the relation between XPG and XPD gene variants in the DNA repair system and oral squamous cell cancers. A total of 111 patients with a pathologic diagnosis of oral squamous cell carcinoma and a control group of 148 healthy volunteers who presented to Istanbul Faculty of Medicine, Department of Otolaryngology & Head and Neck Surgery and Dentistry Faculty were included in the study. Isolation of DNA was achieved using an Invitrogen Purelink Genomic DNA Kit. XPD alleles of Lys751Gln (rs13181) and XPG Asp1104His (rs17655) loci from genomic DNA samples were reproduced using polymerase chain reaction. A statistically significant difference in XPD genotype distribution between control and patient groups was determined (P=0.019). XPD Lys+ was significantly more common in the patient group than in the control group, and a two-fold increased risk for disease was determined. XPD Gln/Gln+ was significantly more common in the control group than in the patient group, and a two-fold decrease in risk for disease was determined (P=0.045). In the other region of the study, there was no statistically significant difference in terms of disease development between XPG genotypes. In conclusion, Lys751Gln polymorphism in the XPD gene could play a role in oral squamous cell development. It is important to increase the numbers of subjects in patient groups and healthy controls in studies to increase the possibility of determining XPD's potential as a molecular risk factor.

Fisher RP
Cdk7: a kinase at the core of transcription and in the crosshairs of cancer drug discovery.
Transcription. 2019; 10(2):47-56 [PubMed] Article available free on PMC after 06/12/2019 Related Publications
The transcription cycle of RNA polymerase II (Pol II) is regulated by a set of cyclin-dependent kinases (CDKs). Cdk7, associated with the transcription initiation factor TFIIH, is both an effector CDK that phosphorylates Pol II and other targets within the transcriptional machinery, and a CDK-activating kinase (CAK) for at least one other essential CDK involved in transcription. Recent studies have illuminated Cdk7 functions that are executed throughout the Pol II transcription cycle, from promoter clearance and promoter-proximal pausing, to co-transcriptional chromatin modification in gene bodies, to mRNA 3´-end formation and termination. Cdk7 has also emerged as a target of small-molecule inhibitors that show promise in the treatment of cancer and inflammation. The challenges now are to identify the relevant targets of Cdk7 at each step of the transcription cycle, and to understand how heightened dependence on an essential CDK emerges in cancer, and might be exploited therapeutically.

Jin D, Zhang M, Hua H
Impact of polymorphisms in DNA repair genes XPD, hOGG1 and XRCC4 on colorectal cancer risk in a Chinese Han Population.
Biosci Rep. 2019; 39(1) [PubMed] Article available free on PMC after 06/12/2019 Related Publications
BACKGROUND: This research aimed to study the associations between XPD (G751A, rs13181), hOGG1 (C326G, rs1052133) and XRCC4 (G1394T, rs6869366) gene polymorphisms and the risk of colorectal cancer (CRC) in a Chinese Han population.
METHOD: A total of 225 Chinese Han patients with CRC were selected as the study group, and 200 healthy subjects were recruited as the control group. The polymorphisms of XPD G751A, hOGG1 C326G and XRCC4 G1394T loci were detected by the RFLP-PCR technique in the peripheral blood of all subjects.
RESULTS: Compared with individuals carrying the XPD751 GG allele, the A allele carriers (GA/AA) had a significantly increased risk of CRC (adjusted OR = 2.109, 95%CI = 1.352-3.287,
CONCLUSION: Our results suggest that XPD G751A, hOGG1 C326G and XRCC4 G1394T gene polymorphisms might play an important role in colorectal carcinogenesis and increase the risk of developing CRC in the Chinese Han population. The interaction between smoking and these gene polymorphisms would increase the risk of CRC.

Ding H, Wen Z, Sun G
Silencing of Xeroderma Pigmentosum Group D Gene Promotes Hepatoma Cell Growth by Reducing P53 Expression.
Med Sci Monit. 2018; 24:8015-8021 [PubMed] Article available free on PMC after 06/12/2019 Related Publications
BACKGROUND This study investigated the effect of xeroderma pigmentosum group D (XPD) silencing on the growth of hepatoma cells and assessed the mechanisms. MATERIAL AND METHODS XPD gene was silenced by siRNA in hepatoma cells. The experiments were randomly divided into a control group, a liposome control group, a negative control (NC) group, an XPD siRNA group, and an XPD siRNA + P53 inhibitor group. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) was used to detect cell viability 24 h after gene silencing and treatments. Terminal deoxynucleotidyl transferases (TdT)-mediated dUTP nick-end labeling (TUNEL) and flow cytometry were used to detect apoptosis. Invasive ability was detected by Transwell assay. Additionally, the expression of mouse double-minute 2 homolog (Mdm2), mouse double-minute 4 homolog (Mdm4), CyclinD1, P21, Bax, P53, C-sis, and Bcl-2 was detected by real-time polymerase chain reaction and Western blotting. RESULTS Compared with the NC group, XPD siRNA significantly reduced XPD expression at both mRNA and protein levels. XPD siRNA significantly promoted cell proliferation, reduced apoptosis, and promoted cell invasive ability. Expression of CyclinD1, Bcl-2, and C-sis increased significantly after XPD silencing, while the expression of P21, Mdm2, Mdm4, Bax, and P53 significantly decreased (vs. NC, P<0.05). Importantly, P53 inhibitor (1 μM bpV) further enhanced the effect of XPD silencing (vs. XPD silencing, P<0.05). CONCLUSIONS Our data revealed that XPD silencing promoted growth of hepatoma cells by reducing P53 expression.

Pietzak EJ, Zabor EC, Bagrodia A, et al.
Genomic Differences Between "Primary" and "Secondary" Muscle-invasive Bladder Cancer as a Basis for Disparate Outcomes to Cisplatin-based Neoadjuvant Chemotherapy.
Eur Urol. 2019; 75(2):231-239 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care for patients with muscle-invasive bladder cancer (MIBC). It is unknown whether this treatment strategy is appropriate for patients who progress to MIBC after treatment for prior noninvasive disease (secondary MIBC).
OBJECTIVE: To determine whether clinical and genomic differences exist between primary and secondary MIBC treated with NAC and RC.
DESIGN, SETTING, AND PARTICIPANTS: Clinicopathologic outcomes were compared between 245 patients with clinical T2-4aN0M0-stage primary MIBC and 43 with secondary MIBC treated with NAC and RC at Memorial Sloan Kettering Cancer Center (MSKCC) from 2001 to 2015. Genomic differences were assessed in a retrospective cohort of 385 prechemotherapy specimens sequenced by whole-exome or targeted exon capture by the Cancer Genome Atlas or at MSKCC. Findings were confirmed in an independent validation cohort of 94 MIBC patients undergoing prospective targeted exon sequencing at MSKCC.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Pathologic response rates, recurrence-free survival (RFS), bladder cancer-specific survival (CSS), and overall survival (OS) were measured. Differences in somatic genomic alteration rates were compared using Fisher's exact test and the Benjamini-Hochberg false discovery rate method.
RESULTS AND LIMITATIONS: Patients with secondary MIBC had lower pathologic response rates following NAC than those with primary MIBC (univariable: 26% vs 45%, multivariable: odds ratio=0.4 [95% confidence interval=0.18-0.84] p=0.02) and significantly worse RFS, CSS, and OS. Patients with secondary MIBC treated with NAC had worse CSS compared with cystectomy alone (p=0.002). In a separate genomic analysis, we detected significantly more likely deleterious somatic ERCC2 missense mutations in primary MIBC tumors in both the discovery (10.9% [36/330] vs 1.8% [1/55], p=0.04) and the validation (15.7% [12/70] vs 0% [0/24], p=0.03) cohort.
CONCLUSIONS: Patients with secondary MIBC treated with NAC had worse clinical outcomes than similarly treated patients with primary MIBC. ERCC2 mutations predicted to result in increased cisplatin sensitivity were enriched in primary versus secondary MIBC. Prospective validation is still needed, but given the lack of clinical benefit with cisplatin-based NAC in patients with secondary MIBC, upfront RC or enrollment in clinical trials should be considered.
PATIENT SUMMARY: A retrospective cohort study of patients with "primary" and "secondary" muscle-invasive bladder cancer (MIBC) treated with chemotherapy before surgical removal of the bladder identified lower response rates and shorter survival in patients with secondary MIBC. Tumor genetic sequencing of separate discovery and validation cohorts revealed that chemotherapy-sensitizing DNA damage repair gene mutations occur predominantly in primary MIBC tumors and may underlie the greater sensitivity of primary MIBC to chemotherapy. Prospective validation is still needed, but patients with secondary MIBC may derive greater benefit from upfront surgery or enrollment in clinical trials rather than from standard chemotherapy.

Tong Y, Xiang Y, Li B, et al.
Association of ERCC2 Gene Polymorphisms with Susceptibility to Diffuse Large B-Cell Lymphoma.
Med Sci Monit. 2018; 24:7015-7022 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
BACKGROUND The objective of this study was to detect the association between ERCC excision repair 2, TFIIH core complex helicase subunit (ERCC2) gene polymorphisms and diffuse large B-cell lymphoma (DLBCL) susceptibility. MATERIAL AND METHODS This study used a case-control design. ERCC2 gene rs1799793 (Asp312Asn) and rs13181 (Lys751Gln) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) both in DLBCL patients and healthy controls. The association between ERCC2 gene polymorphisms and DLBCL risk was assessed by χ² test. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were used to address the association strength. Subgroup analyses were also performed to investigate the genetic effects of ERCC2 polymorphisms on clinical characteristics of DLBCL patients. RESULTS A significant association was discovered between the rs1799793 A allele and increased DLBCL risk (P=0.031, OR=1.928, 95% CI=1.052-3.534). The C allele of rs13181 was obviously associated with elevated DLBCL susceptibility (P=0.047, OR=1.820, 95% CI=1.002-3.305). The subgroup analysis demonstrated that rs1799793 and rs13181 polymorphisms had no relationship with serum lactate dehydrogenase level, nidus number, B-symptoms, Ann Arbor stages, or immunological types in DLBCL cases (P>0.05 for all). CONCLUSIONS Minor allele carriers of ERCC2 gene rs1799793 (Asp312Asn) and rs13181 (Lys751Gln) polymorphisms had higher susceptibility to DLBCL.

Nissar B, Kadla SA, Khan NS, et al.
DNA Repair Gene XRCC1 and XPD Polymorphisms and Gastric Cancer Risk: A Case-Control Study Outcome from Kashmir, India.
Anal Cell Pathol (Amst). 2018; 2018:3806514 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
Coding polymorphisms in several DNA repair genes have been reported to affect the DNA repair capacity and are associated with genetic susceptibility to many human cancers, including gastric cancer. An understanding of these DNA repair gene polymorphisms might assess not only the risk of humans exposed to environmental carcinogens but also their responses to different therapeutical approaches, which target the DNA repair pathway. In the present study, polymorphic variants of two DNA repair genes, XRCC1 Arg399Gln and XPD Lys751Gln, were chosen to be studied in association with gastric cancer susceptibility in the Kashmiri population. A total of 180 confirmed cases of gastric cancer (GC) and 200 hospital-based controls from Government Shri Maharaja Hari Singh Hospital, Srinagar, were included in the study. The genotyping for XRCC1 and XPD genes was carried out by polymerase chain reaction-restriction fragment length polymorphism. We found that tobacco smoking is strongly associated with GC risk (OR = 25.65; 95% CI: 5.49-119.7). However, we did not find any association of polymorphism of XRCC1 Arg399Gln (OR = 1.56; 95% CI: 0.32-7.82) and XPD Lys751Gln (OR = 0.46; CI: 0.10-2.19) with GC risk in the study population. The combination of genotypes and gender stratification of XRCC1 and XPD genotypic frequency did not change the results. Consumption of large volumes of salt tea was also not associated with gastric cancer risk. Polymorphic variants of XRCC1 Arg399Gln and XPD Lys751Gln are not associated with the risk of gastric cancer in the Kashmiri population. However, replicative studies with larger sample size are needed to substantiate the findings.

Smolarz B, Michalska MM, Samulak D, et al.
Studies of Correlations Between Single Nucleotide Polymorphisms of DNA Repair Genes and Endometrial Cancer in Polish Women.
Anticancer Res. 2018; 38(9):5223-5229 [PubMed] Related Publications
AIM: The goals of this study included an analysis of the incidence of single nucleotide polymorphisms (SNPs) genotypes and alleles in DNA repair genes and evaluation of the effects by which this genetic variability may influence the risk for endometrial cancer.
MATERIALS AND METHODS: The study group included 610 women with endometrial cancer and was compared with a quantitatively matched control group of 610 women without any diagnosed malignancy. The following polymorphisms were analyzed: X-Ray repair cross complementing 1 (XRCC1)-Arg399Gln (rs25487); XRCC2-Arg188His (rs3218536); XRCC3-Thr241Met (rs861539); ERCC excision repair 2, TFIIH core complex helicase subunit (ERCC2)-Lys751Gln (rs13181); and 8-oxoguanine DNA glycosylase (OGG1)-Ser326Cys (rs13181).
RESULTS: Allele XRCC2-188His [odds ratio (OR)=5.24, 95% confidence interval (CI)=4.36-6.29; p<0.0001], hOGG1-326Cys (OR=1.60, 95% CI=1.36-1.88; p<0.0001) and ERCC2-751Gln (OR=1.67, 95% CI=1.42-1.96; p<0.0001) strongly correlated with neoplastic disease.
CONCLUSION: The evaluated SNPs may be approached as a group of new risk factors for the development of this cancer type.

Aravind Kumar M, Naushad SM, Narasimgu N, et al.
Whole exome sequencing of breast cancer (TNBC) cases from India: association of MSH6 and BRIP1 variants with TNBC risk and oxidative DNA damage.
Mol Biol Rep. 2018; 45(5):1413-1419 [PubMed] Related Publications
Whole exome sequencing in triple negative breast cancer cases (n = 8) and targeted sequencing in healthy controls (n = 48) revealed BRIP1 rs552752779 (MAF: 75% vs. 6.25%, OR 45.00, 95% CI 9.43-243.32), ERBB2 rs527779103 (MAF: 62.5% vs. 7.29%, OR 21.19, 95% CI 5.11-94.32), ERCC2 rs121913016 (MAF: 56.25% vs. 7.29%, OR 16.34, 95% CI 4.02-70.41), MSH6 rs2020912 (MAF: 56.25% vs. 1.04%, OR 122.13, 95% CI 12.29-2985.48) as risk factors for triple negative breast cancer. Construction of classification and regression tree followed by smart pruning identified MSH6 and BRIP1 variants as the major determinants of TNBC (Triple Negative Breast Cancer) risk. Except for ERBB2, all other genes regulate DNA repair and chromosomal integrity. In TNBC cases, two likely pathogenic variations i.e. NCOR1 rs562300336 and PIM1 rs746748226 were observed at frequencies of 18.75% and 12.5%, respectively. Among the 24 variants of unknown significance, MMP9 rs199676062, SYNE1 rs368709678, AURKA rs373550419, ABCC4 rs11568694 have variant allele frequency ≥ 62.5%. These genes regulate metastasis, nuclear modeling, cell cycle and cellular detoxification, respectively. To conclude, aberrations in DNA mismatch repair, nucleotide excision repair or BRCA1 associated genome surveillance mechanism contribute towards triple negative breast cancer.

Zhang R, Zhou F, Cheng L, et al.
Genetic variants in nucleotide excision repair pathway predict survival of esophageal squamous cell cancer patients receiving platinum-based chemotherapy.
Mol Carcinog. 2018; 57(11):1553-1565 [PubMed] Related Publications
The benefits of platinum-based chemotherapy (PBC) on survival of esophageal squamous cell carcinoma (ESCC) patients are inexplicit due to the varied therapeutic effects. Nucleotide excision repair (NER) pathway plays a vital role in removing platinum-DNA adducts in tumor cells and hence may modulate the therapeutic effect and survival outcome. The present study assessed the associations of 26 potentially functional regulatory single nucleotide polymorphisms (rSNPs) in nine core NER genes with disease-free survival (DFS) and overall survival (OS) in 339 ESCC patients. We found that ERCC2 rs2097215 T and rs3916788 A, ERCC5 rs3759497 A and XPC rs3731054 C alleles were associated with unfavorable DFS. Patients carrying high-risk allele group (HRG, 5-8 risk alleles) had a significantly shorter DFS, compared with those carrying low-risk alleles (LRG, 0-4 risk alleles) [adjusted hazards ratio (HR

Obiedat H, Alrabadi N, Sultan E, et al.
The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients.
BMC Med Genet. 2018; 19(1):112 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
BACKGROUND: Cisplatin is one of the major drugs that used in the treatment of osteosarcoma. Cisplatin exerts its function by making cisplatin-DNA adducts culminating in cellular death. These adducts found to be repaired by nucleotide excision repair (NER) pathway. This study aimed to evaluate if polymorphisms in two main genes in the NER pathway, excision repair cross-complementing group 1 and 2 (ERCC1 and ERCC2) could affect the histological response to cisplatin based chemotherapy or clinical outcomes, particularly, event free survival (EFS) and overall survival (OS) rates.
METHOD: ERCC1 (C118T (rs11615) and C8092A (rs3212986)) and ERCC2 (A751C (rs171140) and G312A (rs1799793)) polymorphisms were analysed in 44 patients with osteosarcoma, who were treated with cisplatin based neoadjuvant chemotherapy. DNA was extracted from patient's formalin-fixed paraffin-embedded (FFPE) samples, patient's genotypes were determined by using polymerase chain reaction-restriction fragment length polymorphism PCR-RFLP assay. The distribution of the patients' genotype and the allele frequencies were reported. The association between each of these genotypes and many clinical and patho-histological parameters (e.g. EFS, OS and patho-histological response to treatment) was examined. The associations between gender, tumor location, presence of metastasis at diagnosis, histological subtypes, and type of neoadjuvant chemotherapy and between the histological response, EFS and OS rates were also examined.
RESULTS: This study revealed that there was a positive and significant association between ERCC1 C8092 A genotypes and median EFS rate in years; patients who were carriers of C allele (CC & CA) were found to have longer EFS rates than patients with AA genotype (P value = 0.006) and the median EFS rates were respectively as following: 2.04, 0.24 years. As well, both the presence of metastasis and the histological subtype at the time of diagnosis, were able to affect the EFS rate but not the OS. However, there was a positive correlation between OS rate and the patients' primary response to treatment.
CONCLUSIONS: Our results suggested that ERCC1 8092 C allele may play a role as a candidate prognostic marker in patients with osteosarcoma.

Galande AA, Perween N, Saijo M, et al.
Analysis of the conserved NER helicases (XPB and XPD) and UV-induced DNA damage in Hydra.
Biochim Biophys Acta Gen Subj. 2018; 1862(9):2031-2042 [PubMed] Related Publications
BACKGROUND: Nucleotide excision repair (NER) pathway is an evolutionarily conserved mechanism of genome maintenance. It detects and repairs distortions in DNA double helix. Xeroderma Pigmentosum group B (XPB) and group D (XPD) are important helicases in NER and are also critical subunits of TFIIH complex. We have studied XPB and XPD for the first time from the basal metazoan Hydra which exhibits lack of organismal senescence.
METHODS: In silico analysis of proteins was performed using MEGA 6.0, Clustal Omega, Swiss Model, etc. Gene expression was studied by in situ hybridization and qRT-PCR. Repair of CPDs was studied by DNA blot assay. Interactions between proteins were determined by co- immunoprecipitation. HyXPB and HyXPD were cloned in pET28b, overexpressed and helicase activity of purified proteins was checked.
RESULTS: In silico analysis revealed presence of seven classical helicase motifs in HyXPB and HyXPD. Both proteins revealed polarity-dependent helicase activity. Hydra repairs most of the thymine dimers induced by UVC (500 J/m2) by 72 h post-UV exposure. HyXPB and HyXPD transcripts, localized all over the body column, remained unaltered post-UV exposure indicating their constitutive expression. In spite of high levels of sequence conservation, XPB and XPD failed to rescue defects in human XPB- and XPD-deficient cell lines. This was due to their inability to get incorporated into the TFIIH multiprotein complex.
CONCLUSIONS: Present results along with our earlier work on DNA repair proteins in Hydra bring out the utility of Hydra as model system to study evolution of DNA repair mechanisms in metazoans.

Ban EZ, Lye MS, Chong PP, et al.
Association of hOGG1 Ser326Cys, ITGA2 C807T, TNF-A -308G>A and XPD Lys751Gln polymorphisms with the survival of Malaysian NPC patients.
PLoS One. 2018; 13(6):e0198332 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
BACKGROUND: Nasopharyngeal carcinoma is a rare form of cancer across the world except in certain areas such as Southern China, Hong Kong and Malaysia. NPC is considered a relatively radiosensitive tumor and patients diagnosed at early stages tend to survive longer compared to those with advanced disease. Given that early symptoms of NPC are non-specific and that the nasopharynx is relatively inaccessible, less invasive screening methods such as biomarker screening might be the key to improve NPC survival and management. A number of genes with their respective polymorphisms have been shown in past studies to be associated with survival of various cancers. hOGG1 and XPD genes encode for a DNA glycosylase and a DNA helicase respectively; both are proteins that are involved in DNA repair. ITGA2 is the alpha subunit of the transmembrane receptor integrin and is mainly responsible for cell-cell and cell-extracellular matrix interaction. TNF-α is a cytokine that is released by immune cells during inflammation.
METHODS: Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to genotype all the aforementioned gene polymorphisms. Kaplan-Meier survival function, log-rank test and Cox regression were used to investigate the effect of gene polymorphisms on the all-cause survival of NPC.
RESULTS: NPC cases carrying T/T genotype of ITGA2 C807T have poorer all-cause survival compared to those with C/C genotypes, with an adjusted HR of 2.06 (95% CI = 1.14-3.72) in individual model. The 5-year survival rate of C/C carriers was 55% compared to those with C/T and T/T where the survival rates were 50% and 43%, respectively.
CONCLUSION: The finding from the present study showed that ITGA2 C807T polymorphism could be potentially useful as a prognostic biomarker for NPC. However, the prognostic value of ITGA2 C807T polymorphism has to be validated by well-designed further studies with larger patient numbers.

Mucha B, Pytel D, Markiewicz L, et al.
Nucleotide Excision Repair Capacity and XPC and XPD Gene Polymorphism Modulate Colorectal Cancer Risk.
Clin Colorectal Cancer. 2018; 17(2):e435-e441 [PubMed] Related Publications
BACKGROUND: Colorectal cancer (CRC) is leading malignant tumors to occur mainly in industrialized countries, where it exhibits one of the highest mortality rates. Up to 80% of all CRCs characterize a chromosomal instability (CIN) phenotype. The main challenge faced by scientist is to reveal the mechanism of CIN development. An often proposed model is defects in DNA repair in terms of efficiency and genetic variations that modulate the response to stimuli from the environment. The objectives of this research were to determine whether nucleotide excision repair (NER) might affect CRC risk.
MATERIALS AND METHODS: The first part of the study concerns NER efficiency. In the second part we selected 2 common single nucleotide polymorphisms within genes involved in NER (Xeroderma pigmentosum group C (XPC) Lys939Gln, Xeroderma pigmentosum group D (XPD) Lys751Gln) to determine the relation between them and CRC risk. The restriction fragment length polymorphism-polymerase chain reaction method was used for genotyping of 221 CRC patients vs. 270 cancer-free individuals. The isotopic labeling in vitro assay was used to evaluate NER capacity in lymphocytes and tissue protein extracts.
RESULTS: We observed a significantly decreased level of NER capacity (P = .025) in lymphocytes delivered from CRC patients compared with healthy ones. Polymorphism screening points to higher CRC risk for the Gln939Gln genotype (P = .02) and Gln allele (P = .002) of the XPC gene.
CONCLUSION: Taken together, our findings suggest a potential role for NER in CRC.

Zhou X, Zeng Y, Jiang H, et al.
Predictive value of excision repair cross-complementing group 2 gene Lys751Gln and Asp312Asn polymorphisms in melanoma risk.
Melanoma Res. 2018; 28(4):311-318 [PubMed] Related Publications
Epidemiological studies have assessed the association between excision repair cross-complementing group 2 (ERCC2) Lys751Gln and Asp312Asn polymorphisms and melanoma risk with conflicting results. Relevant articles were searched from PubMed, Embase, and Web of Science with a time limit of 3 September 2016. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. We performed this meta-analysis with 12 studies including 6157 cases and 8873 controls for Lys751Gln and nine studies including 5037 cases and 7542 controls for Asp312Asn polymorphism. Overall, no significant associations were found under all the models for Lys751Gln polymorphism, and significant associations were found for Asp312Asn polymorphism for AA versus GG (OR=1.12, 95% CI=1.00-1.26) and for the recessive model (OR=1.11, 95% CI=1.00-1.24). In the stratification analyses by source of control: for Lys751Gln polymorphism, significant associations were found for CC versus AA (OR=1.19, 95% CI=1.04-1.36) and the recessive model (OR=1.15, 95% CI=1.02-1.30); for Asp312Asn polymorphism, significant associations were found for AA versus GG (OR=1.31, 95% CI=1.11-1.53) and the recessive model (OR=1.29, 95% CI=1.11-1.50). This meta-analysis suggested that both the Lys751Gln and Asp312Asn polymorphisms were risk factors for melanoma risk in population-based subgroup.

Jóźwik M, Posmyk R, Jóźwik M, et al.
Breast cancer in an 18-year-old female: A fatal case report and literature review.
Cancer Biol Ther. 2018; 19(7):543-548 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
Breast cancer (BC) is the most frequent malignancy in both pre- and postmenopausal women. However, it is exceedingly rare in very young patients, and especially in adolescents. Herein, we report a case of an 18-year-old female diagnosed with invasive BC. The proband had been found to be negative for BC in close family members. A common BC genetic screening test for the Polish population did not detect any known founder mutations in the BRCA1 gene. Further evaluation identified a p.Ile157Thr (I157T) mutation in the CHEK2 gene, a p.Ala1991Val (A1991V) variant of unknown significance in the BRCA2 gene, p.Lys751Gln (K751Q) variant in the XPD (ERCC2) gene, and a homozygous p.Glu1008Ter (E1008*) mutation in the NOD2 gene. No other mutation had been found by next generation sequencing in major BC high-risk susceptibility genes BRCA1, BRCA2, as well as 92 other genes. To date, all these found alterations have been considered as low to moderate risk factors in the general population and moderate risk factors in younger women (<35 years of age). There are no previous articles relating low and moderate risk gene mutations to very young onset (below 20 years) BC with a fatal outcome. In our patient, a possible cumulative or synergistic risk effect for these 4 alterations, and a mutation in the NOD2 gene in particular, of which both presumably healthy parents were found to be carriers, is suggested.

Yehia L, Ni Y, Sesock K, et al.
Unexpected cancer-predisposition gene variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome patients without underlying germline PTEN mutations.
PLoS Genet. 2018; 14(4):e1007352 [PubMed] Article available free on PMC after 01/02/2020 Related Publications
Patients with heritable cancer syndromes characterized by germline PTEN mutations (termed PTEN hamartoma tumor syndrome, PHTS) benefit from PTEN-enabled cancer risk assessment and clinical management. PTEN-wildtype patients (~50%) remain at increased risk of developing certain cancers. Existence of germline mutations in other known cancer susceptibility genes has not been explored in these patients, with implications for different medical management. We conducted a 4-year multicenter prospective study of incident patients with features of Cowden/Cowden-like (CS/CS-like) and Bannayan-Riley-Ruvalcaba syndromes (BRRS) without PTEN mutations. Exome sequencing and targeted analysis were performed including 59 clinically actionable genes from the American College of Medical Genetics and Genomics (ACMG) and 24 additional genes associated with inherited cancer syndromes. Pathogenic or likely pathogenic cancer susceptibility gene alterations were found in 7 of the 87 (8%) CS/CS-like and BRRS patients and included MUTYH, RET, TSC2, BRCA1, BRCA2, ERCC2 and HRAS. We found classic phenotypes associated with the identified genes in 5 of the 7 (71.4%) patients. Variant positive patients were enriched for the presence of second malignant neoplasms compared to patients without identified variants (OR = 6.101, 95% CI 1.143-35.98, p = 0.035). Germline variant spectrum and frequencies were compared to The Cancer Genome Atlas (TCGA), including 6 apparently sporadic cancers associated with PHTS. With comparable overall prevalence of germline variants, the spectrum of mutated genes was different in our patients compared to TCGA. Intriguingly, we also found notable enrichment of variants of uncertain significance (VUS) in our patients (OR = 2.3, 95% CI 1.5-3.5, p = 0.0002). Our data suggest that only a small subset of PTEN-wildtype CS/CS-like and BRRS patients could be accounted for by germline variants in some of the known cancer-related genes. Thus, the existence of alterations in other and more likely non-classic cancer-associated genes is plausible, reflecting the complexity of these heterogeneous hereditary cancer syndromes.

Zhao Z, Zhang A, Zhao Y, et al.
The association of polymorphisms in nucleotide excision repair genes with ovarian cancer susceptibility.
Biosci Rep. 2018; 38(3) [PubMed] Article available free on PMC after 01/02/2020 Related Publications
Nucleotide excision repair (NER), the core mechanism of DNA repair pathway, was commonly used to maintain genomic stability and prevent tumorigenesis. Previous investigations have demonstrated that single nucleotide polymorphisms (SNPs) of NER pathway genes were associated with various types of cancer. However, there was no research elucidating the genetic association of entire NER pathway with ovarian cancer susceptibility. Therefore, we conducted genotyping for 17 SNPs of six NER core genes (

Fathi Z, Syn NL, Zhou JG, Roudi R
Molecular epidemiology of lung cancer in Iran: implications for drug development and cancer prevention.
J Hum Genet. 2018; 63(7):783-794 [PubMed] Related Publications
Epidemiological studies undertaken over the past decades reveal a gradual but progressive increase in the incidence and mortality attributable to lung cancer in the Islamic Republic of Iran, a sovereign state geographically situated at the crossroads of Central Eurasia and Western Asia. We identified references published in English and Persian through searches of PubMed, EMBASE, Web of Science, Scopus, and the Scientific Information Database (SID)-a specialized Iranian database, which indexes Iranian scientific journals-between inception and 15 September 2017. Of 1475 references identified through electronic searches, we reviewed the full text of 88 studies, and included 38 studies in the review. Potentially druggable NSCLC targets, which have been studied in Iran include EGFR, ALK, ERBB2, and KIT; but no studies were found, which examined the impact of MET, ROS1, BRAF, PIK3CA, and FGFR1 aberrations. We were able to identify some literature on DNA repair genes and xenobiotic metabolism, including TP53, TP63, ERCC2, XRCC2, SIRT1, PTEN, CYP1A1, CYP1B1, GSTT1, and GSTM1. We also found an increasing amount of research performed in relation to the tumor microenvironment and immune contexture, including CTLA4, MAGE, FOXP3, IFN-γ, and various interleukins, chemokines, and transcription factors; but did not identify any publication concerning the expression of PD-1/PD-L1 in lung cancer. Our survey of research performed in Iran has revealed a dearth of studies in topics, which are otherwise highly pursued in developed countries, but nevertheless, has begun to hint at a distinct biology of lung cancer in this part of the world.

Pérez-Ramírez C, Cañadas-Garre M, Alnatsha A, et al.
Pharmacogenetics of platinum-based chemotherapy: impact of DNA repair and folate metabolism gene polymorphisms on prognosis of non-small cell lung cancer patients.
Pharmacogenomics J. 2019; 19(2):164-177 [PubMed] Related Publications
Chemotherapy based on platinum compounds is the standard treatment for NSCLC patients with EGFR wild type, and is also used as second line in mutated EGFR patients. Nevertheless, this therapy presents poor clinical outcomes. ERCC1, ERCC2, XRCC1, MDM2, MTHFR, MTR, and SLC19A1 gene polymorphisms may contribute to individual variation in response and survival to platinum-based chemotherapy. The aim of this study was to investigate the influence of these polymorphisms on response and survival of NSCLC patients treated with platinum-based chemotherapy. A retrospective-prospective cohorts study was conducted, including 141 NSCLC patients. Polymorphisms were analyzed by PCR real-time with Taqman® probes. Patients with ERCC1 rs3212986-GG (p = 0.0268; OR = 2.50; CI

Lotan Y, Woldu SL, Sanli O, et al.
Modelling cost-effectiveness of a biomarker-based approach to neoadjuvant chemotherapy for muscle-invasive bladder cancer.
BJU Int. 2018; 122(3):434-440 [PubMed] Article available free on PMC after 01/09/2019 Related Publications
OBJECTIVES: To model the cost-effectiveness of a biomarker-based approach to select patients for neoadjuvant chemotherapy (NAC) before radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC).
PATIENTS AND METHODS: We obtained data from the most recent clinical studies on patients with locally advanced MIBC treated by RC, including stage distributions, overall survival (OS) estimates, associated costs, and utilisation/response to NAC. Additionally, we estimated the putative efficacy of three biomarkers to select patients for NAC: DNA-repair gene panel [ataxia telangiectasia mutated (ATM), retinoblastoma 1 (RB1), and Fanconi anaemia complementation group C (FANCC)], excision repair cross-complementation group 2 (ERCC2), and ribonucleic acid (RNA) subtypes. A decision analysis model was developed to evaluate the cost-effectiveness of biomarker-based approaches to select patients with MIBC for NAC. Comparison of cost-effectiveness included RC alone, unselected NAC plus RC, and NAC based on the three aforementioned biomarkers.
RESULTS: The DNA-repair gene panel-based approach to NAC was the most cost-effective strategy (mean OS of 3.14 years, $31 482/life year). Under this approach, 38% would undergo NAC, about twice the number of patients who are currently receiving NAC for MIBC. Such an approach would improve mean OS by 5.2, 1.6, and 4.4 months compared to RC alone, a hypothetical scenario where all patients received NAC, and compared to current estimates of NAC utilisation, respectively.
CONCLUSIONS: A biomarker-based strategy to identify patients with MIBC who should undergo NAC was more cost-effective than unselected use of NAC or RC alone. As further data becomes available, such a model may serve as a basis for incorporating biomarkers into clinical decision making.

Liao WY, Ho CC, Tsai TH, et al.
Combined effect of ERCC1 and ERCC2 polymorphisms on overall survival in non-squamous non-small-cell lung cancer patients treated with first-line pemetrexed/platinum.
Lung Cancer. 2018; 118:90-96 [PubMed] Related Publications
OBJECTIVES: Polymorphisms of DNA repair genes may affect DNA repair capacity and the sensitivity of platinum doublets chemotherapy in non-small-cell lung cancer (NSCLC). We prospectively evaluated whether single nucleotide polymorphisms (SNPs) of ERCC1, ERCC2, XRCC1, and XRCC3 were associated with treatment outcome in advanced non-squamous NSCLC patients receiving pemetrexed/platinum as their first-line chemotherapy.
MATERIALS AND METHODS: Genotyping of six SNPs in four DNA repair genes in 58 patients treated with first-line pemetrexed/platinum was performed using TaqMan SNP Genotyping Assays.
RESULTS: The wild-type ERCC1 8092 (C/C) was significantly associated with a better objective response compared to the variant genotypes (C/A + A/A) (48% vs 10%, P = .005). In the multivariate Cox proportional hazards model, we found that individuals with a wild-type genotype of ERCC1 Asn118Asn, ERCC1 C8092A and ERCC2 Asp312Asn had significantly better overall survival (OS) than those with a heterozygous or homozygous variant genotype. On the other hand, the heterozygous variant genotype of ERCC2 Lys751Gln was associated with better OS than that of the wild-type genotype. We further explored the combined effect of SNPs on OS, and found a significant allele/dose-dependent trend toward decreasing OS in patients with an increasing number of unfavorable alleles among four SNPs in ERCC1 and ERCC2. The median OS of patients with two or three unfavorable alleles (30.1 and 30.5 months, respectively) was significantly longer than that of patients with 4 unfavorable alleles (11.8 months, log-rank test for trend, P = .001).
CONCLUSION: A combination of ERCC1 and ERCC2 polymorphisms may predict OS among pemetrexed/platinum treated advanced non-squamous NSCLC patients.

Liu J, Li H, Sun L, et al.
The Differential Expression of Core Genes in Nucleotide Excision Repair Pathway Indicates Colorectal Carcinogenesis and Prognosis.
Biomed Res Int. 2018; 2018:9651320 [PubMed] Article available free on PMC after 01/09/2019 Related Publications
Background: Nucleotide excision repair (NER) plays a critical role in maintaining genome integrity. This study aimed to investigate the expression of NER genes and their associations with colorectal cancer (CRC) development.
Method: Expressions of NER genes in CRC and normal tissues were analysed by ONCOMINE. The Cancer Genome Atlas (TCGA) data were downloaded to explore relationship of NER expression with clinicopathological parameters and survival of CRC.
Results: ERCC1, ERCC2, ERCC5, and DDB2 were upregulated while ERCC4 was downregulated in CRC. For colon cancer, high ERCC3 expression was related to better T stage; ERCC5 expression indicated deeper T stage and distant metastasis; DDB2 expression suggested earlier TNM stage. For rectal cancer, ERCC2 expression correlated with favourable T stage; XPA expression predicted worse TNM stage. ERCC2 expression was associated with worse overall survival (OS) in colon cancer (HR = 1.53,
Conclusion: ERCC1, ERCC2, ERCC4, ERCC5, and DDB2 were differently expressed in CRC and normal tissues; ERCC2, ERCC3, ERCC5, XPA, and DDB2 correlated with clinicopathological parameters of CRC, while ERCC2, ERCC4, and XPC might predict CRC prognosis.

Liu OG, Xiong XY, Li CM, et al.
Role of Xeroderma Pigmentosum Group D in Cell Cycle and Apoptosis in Cutaneous Squamous Cell Carcinoma A431 Cells.
Med Sci Monit. 2018; 24:453-460 [PubMed] Article available free on PMC after 01/09/2019 Related Publications
BACKGROUND Cutaneous squamous cell carcinoma (cSCC) is the second most widespread cancer in humans and its incidence is rising. Novel therapy with better efficacy is needed for clinical treatment of cSCC. Many studies have shown the importance of DNA repair pathways during the development of cancer. A key nucleotide excision repair (NER) protein, xeroderma pigmentosum group D (XPD), is responsible for the excision of a large variety of bulky DNA lesions. MATERIAL AND METHODS To explore the role of XPD in A431 cells, we overexpressed XPD in A431 cells and performed MTT assay, flow cytometry, and Western blot analysis to examine cell proliferation, cell apoptosis, and genes expression. RESULTS We found that the overexpression of XPD suppressed cell viability, induced cell cycle arrest at G1 phase, and promoted cell apoptosis. Additionally, XPD blocked the expression of c-myc, cdc25A, and cdk2, and improved the levels of HIPK2 and p53. CONCLUSIONS These results provide new evidence to reveal the role of XPD in cSCC A431 cells and suggest that XPD may serve as an anti-oncogene during cSCC development.

Hass HG, Vogel U, Scheurlen M, Jobst J
Subclassification and Detection of New Markers for the Discrimination of Primary Liver Tumors by Gene Expression Analysis Using Oligonucleotide Arrays.
Gut Liver. 2018; 12(3):306-315 [PubMed] Article available free on PMC after 01/09/2019 Related Publications
Background/Aims: The failure to correctly differentiate between intrahepatic cholangiocarcinoma (CC) and hepatocellular carcinoma (HCC) is a significant clinical problem, particularly in terms of the different treatment goals for both cancers. In this study a specific gene expression profile to discriminate these two subgroups of liver cancer was established and potential diagnostic markers for clinical use were analyzed.
Methods: To evaluate the gene expression profiles of HCC and intrahepatic CC, Oligonucleotide arrays (
Results: 695 genes/expressed sequence tags (ESTs) in HCC (245 up-/450 down-regulated) and 552 genes/ESTs in CC (221 up-/331 down-regulated) were significantly dysregulated (p<0.05, fold change >2, ≥70%). Using a supervised learning method, and one-way analysis of variance a specific 270-gene expression profile that enabled rapid, reproducible differentiation between both tumors and nonmalignant liver tissues was established. A panel of 12 genes (e.g., HSP90β, ERG1, GPC3, TKT, ACLY, and NME1 for HCC; SPT2, T4S3, CNX43, TTD1, HBD01 for CC) were detected and partly described for the first time as potential discrimination markers.
Conclusions: A specific gene expression profile for discrimination of primary liver cancer was identified and potential marker genes with feasible clinical impact were described.

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