Excision Repair Cross-complementation Group Research Articles

Association of Chemotherapy Response Score with Multidrug Resistance 1 and CA125 ELIMination Rate Constant K in Patients with Advanced Ovarian Cancer Treated with Neoadjuvant Chemotherapy.

The relationship between chemotherapy response score (CRS), a widely used response predictor of neoadjuvant chemotherapy-interval debulking surgery (NAC-IDS), and multidrug resistance 1 (MDR1) and CA125 ELIMination rate constant K (KELIM), is undetermined. We evaluated CRS in advanced ovarian cancer patients undergoing NAC and looked for associations between CRS and MDR1 and CA125 KELIM. Our aim was to predict the therapeutic effect of NAC before interval debulking surgery (IDS) by examining its association with CRS. This retrospective cohort study included patients who underwent NAC-IDS (first-line treatment) at Kurume University Hospital, Japan, between 2004 and 2017. CRS association with MDR1 and CA125 KELIM was examined using Cox proportional hazard regression analyses. Survival curves used Kaplan-Meier method, and survival differences between groups used log-rank test. Overall, 55 patients were classified into CRS1 (n=22), CRS2 (n=19), and CRS3 (n=14). The CRS3 group had a significantly better prognosis than the CRS1 or CRS2 group. CRS, age, and IDS status were clinical prognostic factors for ovarian cancer. MDR1 positivity for excision repair cross-complementing group 1, β-tubulin, and Y-box binding protein-1 occurred in 15, 17, and 11 patients, respectively, but these were not associated with CRS. CA125 KELIM was <0.5 (n=8), 0.5-1.0 (n=30), and ≥ 1.0 (n=17) but not associated with CRS. CRS is reconfirmed as a treatment response predictor for NAC-IDS, but its association with drug resistance factors remains unconfirmed.

Lung cancer, predictive factor and ERCC1

Introduction: Excision repair cross-complementing group 1 (ERCC1) counteracts the cytotoxic effect of cisplatin through its role in DNA repair, and its expression level is a crucial factor for sensitivity to this drug. The objective of this study was to assess the impact of ERCC1 on tumor response and survival in patients with advanced non-small cell lung cancer (NSCLC) treated with a platinum-based regimen. Methods: Analysis of survival and tumor response based on the expression level of ERCC1 (detected by immunohistochemistry) in a cohort of NSCLC patients followed in a standard care setting. Results: Among the 77 cases of NSCLC included, ERCC1 expression was low in 64.9% of cases and high in 35.1% of cases. In the 52 patients treated with cisplatin, survival and tumor response were better in the low-expression group compared to the high-expression group: 14.35 months versus 9.49 months, p=0.022; Objective Response: 42.4% versus 0%, p=0.001. No significant difference was found based on protein expression level in patients treated with carboplatin. Conclusion: ERCC1 overexpression in patients treated with cisplatin predicts a poor tumor response and shorter survival.

Predictive and prognostic value of excision repair cross-complementing group 1 in patients with advanced gastric cancer

BackgroundTo define the optimal chemotherapy regimen for each patient we therefore used tissue from patients to identify molecular prognostic or predictive biomarkers.MethodsEndoscopic biopsy specimens from primary lesions and surgical specimens on a phase III trial in patients with unresectable advanced or recurrent gastric cancer treated with docetaxel with cisplatin plus S-1 (DCS) or cisplatin plus S-1 (CS), were collected. We measured the mRNA expression of ERCC1 and analyzed SNPs in GSTP1 and ERCC1.ResultsLow ERCC1 expression was associated with favorable prognosis for overall survival, OS by multivariable analysis (P = 0.001). There were significant interactions between the two treatment arms of DCS and CS, and ERCC1 mRNA expression. In patients with low ERCC1 expression of a favorable prognosis, DCS therapy was inferior to CS (P = 0.046). In addition to GSTP1 rs1695 (HR 1.728), ERCC1 rs3212980, ERCC1 rs2298881, ERCC1 rs3212964 with high expression of ERCC1 mRNA were associated with significantly worse prognosis with regard to OS.ConclusionsERCC1 mRNA is an independent prognostic factor and predictive marker that can be used to guide the addition of docetaxel. The SNPs of ERCC1 and GSTP1 could be also prognostic or predictive factors.

XPA tumor variant leads to defects in NER that sensitize cells to cisplatin.

Nucleotide excision repair (NER) reduces efficacy of treatment with platinum (Pt)-based chemotherapy by removing Pt lesions from DNA. Previous study has identified that missense mutation or loss of the NER genes Excision Repair Cross Complementation Group 1 and 2 (ERCC1 and ERCC2) leads to improved patient outcomes after treatment with Pt-based chemotherapies. Although most NER gene alterations found in patient tumors are missense mutations, the impact of mutations in the remaining nearly 20 NER genes is unknown. Towards this goal, we previously developed a machine learning strategy to predict genetic variants in an essential NER protein, Xeroderma Pigmentosum Complementation Group A (XPA), that disrupt repair. In this study, we report in-depth analyses of a subset of the predicted variants, including in vitro analyses of purified recombinant protein and cell-based assays to test Pt agent sensitivity in cells and determine mechanisms of NER dysfunction. The most NER deficient variant Y148D had reduced protein stability, weaker DNA binding, disrupted recruitment to damage, and degradation. Our findings demonstrate that tumor mutations in XPA impact cell survival after cisplatin treatment and provide valuable mechanistic insights to improve variant effect prediction. Broadly, these findings suggest XPA tumor variants should be considered when predicting chemotherapy response.

Prognostic Significance of Excision Repair Cross-Complementation Group 1 on Circulating Tumor Cells for Nasopharyngeal Carcinoma.

Liquid biopsy, including the detection of circulating tumor cells (CTCs), has emerged as a promising tool for cancer diagnosis and monitoring. However, the prognostic value of CTCs in nasopharyngeal carcinoma (NPC) remains unclear due to the lack of phenotypic characterization. The expression of Excision Repair Cross-Complementation Group 1 (ERCC1) and CTCs epithelial-mesenchymal transition (EMT) have been associated with treatment efficacy. In this study, we aimed to evaluate the prognostic significance of ERCC1 expression on CTCs and their EMT subtypes before treatment in NPC. We retrospectively analyzed 108 newly diagnosed locally advanced NPC patients who underwent CanPatrol™ CTC testing between November 2018 and November 2021. CTCs were counted and classified into epithelial, epithelial-mesenchymal hybrid, and mesenchymal subtypes. ERCC1 expression was divided into negative and positive groups. Clinical features and survival outcomes were analyzed. The positive rate of CTCs was 92.6% (100/108), with an ERCC1 positivity rate of 74% (74/100). Further analysis of the subtypes showed that positive ERCC1 on mesenchymal CTCs was associated with a later N stage (P = .01). Positive ERCC1 expression was associated with poor overall survival (OS; P = .039) and disease-free survival (DFS; P = .035). Further analysis of subtypes showed that the positive ERCC1 on mesenchymal-type CTCs was associated with poor OS (P = .012) and metastasis-free survival (MFS; P = .001). Our findings suggest that ERCC1 expression on CTCs may serve as a new prognostic marker for NPC patients. Evaluating CTCs subtypes may become an auxiliary tool for personalized and precise treatment.

CircMAP3K4 Suppresses H2O2-Induced Human Lens Epithelial Cell Injury by miR-630/ERCC6 Axis in Age-Related Cataract

Background Dysregulated circular RNAs (circRNAs) is involved in the pathogenesis of age-related cataract (ARC). Here, this study aimed to explore the function and mechanism of circMAP3K4 in ARC. Methods Human lens epithelial cells were exposed to hydrogen peroxide (H2O2) for functional experiments. qRT-PCR and western blotting analyses were used for the expression detection of genes and proteins. Cell proliferation was tested using cell counting kit-8 and EdU. Flow cytometry was applied to analyze cell apoptosis and cell cycle. The oxidative stress was evaluated by detecting the production of malondialdehyde (MDA), reactive oxygen species (ROS), and superoxide dismutase (SOD). The target relationship between miR-630 and circMAP3K4 or Excision repair cross-complementing group 6 (ERCC6) was analyzed by dual-luciferase reporter assay and RIP assay. Results CircMAP3K4 was lowly expressed in ARC patients and H2O2-induced HLECs. Functionally, forced expression of circMAP3K4 protected HLECs against H2O2-evoked proliferation inhibition, cell cycle arrest and the promotion of cell apoptosis and oxidative stress. Mechanistically, circMAP3K4 acted as a sponge for miR-630 to regulate the expression of its target ERCC6. MiR-630 was highly expressed while ERCC6 was lowly expressed in ARC patients and H2O2-induced HLECs. Up-regulation of miR-630 could reverse the protective effects of circMAP3K4 on HLECs under H2O2 treatment. In addition, inhibition of miR-630 suppressed H2O2-induced HLEC injury, which was abolished by ERCC6 silencing. Conclusion Forced expression of circMAP3K4 protected HLECs against H2O2-evoked apoptotic and oxidative injury via miR-630/ERCC6 axis, suggesting that circMAP3K4 may function as a potential therapeutic target for ARC.

Role of rs873601 Polymorphisms in Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy.

Lung cancer is still the most lethal malignancy in the world, according to the report of Cancer Statistics in 2021. Platinum-based chemotherapy combined with immunotherapy is the first-line treatment in lung cancer patients. However, the 5-year survival rate is always affected by the adverse reactions and drug resistance caused by platinum-based chemotherapy. DNA damage and repair system is one of the important mechanisms that can affect the response to chemotherapy and clinical outcomes in lung cancer patients. The objective of this study is to find the relationship between the polymorphisms of DNA repair genes with the prognosis of platinum-based chemotherapy in lung cancer patients. We performed genotyping in 17 single nucleotide polymorphisms (SNPs) of Excision Repair Cross-Complementation group (ERCC) genes and X-ray Repair Cross-Complementing (XRCC) genes of 345 lung cancer patients via Sequenom MassARRAY. We used Cox proportional hazard models, state, and plink to analyze the associations between SNPs and the prognosis of lung cancer patients. We found that the ERCC5 rs873601 was associated with the overall survival time in lung cancer patients treated with platinum-based chemotherapy (p = 0.031). There were some polymorphisms that were related to the prognosis in specific subgroups of lung cancer. Rs873601 showed a great influence on the prognosis of patients more than 55 years, Small Cell Lung Cancer (SCLC), and smoking patients. Rs2444933 was associated with prognosis in age less than 55 years, SCLC, metastasis, and stage III/IV/ED patients. Rs3740051 played an important role in the prognosis of SCLC and metastasis patients. Rs1869641 was involved in the prognosis of SCLC patients. Rs1051685 was related to the prognosis in non-metastasis patients. The ERCC5 rs873601 (G>A) was a valuable biomarker for predicting the prognosis in lung cancer patients treated with platinum-based chemotherapy.

BRCA1 expression and its combined low expression with PARP1 and ERCC1 predict chemotherapeutic response in ovarian cancer

Objective: This study aimed to evaluate the associations of immunohistochemical expressions of various deoxyribonucleic acid repair proteins, either individually or combined, with the response to platinum-based chemotherapy and overall survival in epithelial ovarian cancer.Material and Methods: This retrospective cohort study included patients with epithelial ovarian cancer who were treated by primary cytoreductive surgery with adjuvant platinum-based chemotherapy at Songklanagarind Hospital between January 2008 and December 2019. Immunohistochemistry analysis of breast cancer type 1 (BRCA1), poly (ADP-ribose) polymerase 1 (PARP1), X-ray repair cross-complementing 1 (XRCC1), and excision repair cross-complementation group 1 (ERCC1) expression was performed. Logistic regression was used to evaluate factors associated with chemotherapeutic response and Cox regression was applied for survival analysis.Results: Chemotherapeutic response was achieved in 205 of 249 patients (82.3%). Low BRCA1 expression was associated with good response (odds ratio [OR] 5.01, 95% confidence interval [CI] 1.78–14.1) and favorable overall survival (hazard ratio 0.61, 95% CI 0.38–0.98). PARP1, XRCC1, and ERCC1 showed no significant predictive or prognostic roles; however, combined low expression of PARP1/BRCA1 (OR 7.62, 95% CI 1.69–34.31) and ERCC1/BRCA1 (OR 6.98, 95% CI 1.5–32.52) additively enhanced response compared to high/high expressions.Conclusion: This study provides evidence that epithelial ovarian cancer (EOC) with low BRCA1 expression is more likely to be responsive to platinum-based therapy and is associated with favorable overall survival compared to tumors with high BRCA1 expression. The study supports a potential therapeutic strategy involving co-depletion of PARP1/BRCA and ERCC1/BRCA1 expression, although additional studies are needed.

Polymorphisms in ERCC1, ERCC4 and ERCC5 genes as biomarkers of susceptibility for pesticide-induced DNA damage in North-West Indian agricultural workers

BackgroundOccupational pesticides exposure has raised health concerns due to genotoxicity and accumulation of DNA damage. Polymorphisms in genes encoding enzymes involved in nucleotide excision repair (NER) may affect the individual’s susceptibility to pesticide toxicity.MethodsThis study evaluates the association of excision repair cross complementation group 1 (ERCC1) (8092 C > A, 3’UTR, rs3212986) and ERCC1 (19007 C > T, Asn118Asn, rs11615), ERCC4 (1244 G > A, Arg415Gln, rs1800067) and ERCC5 (3507 G > C, Asp1104His, rs17655) polymorphisms with pesticide-induced DNA damage in North-West Indian agricultural workers. The study population comprised 225 agricultural workers exposed to pesticides and 225 non-exposed controls.ResultsOur study demonstrate that exposed workers carrying variant ERCC1 8092AA genotype showed higher total comet DNA migration (p = 0.015) as well as increased frequency of cells showing DNA migration (p = 0.027). Exposed agricultural workers with variant ERCC4 1244AA (415Gln/Gln) and ERCC5 3507CC (1104His/His) genotypes exhibited elevation in total comet DNA migration (p < 0.01). However, genotypes of ERCC1 19007 C > T (Asn118Asn) showed no association with total comet DNA migration (p = 0.963), frequency of cells showing DNA migration (p = 0.423) as well as mean tail length (p = 0.432).ConclusionERCC1, ERCC4 and ERCC5 polymorphisms influence DNA damage and can be used as biomarkers of susceptibility for pesticide-induced DNA damage in North-West Indian agricultural workers.

Mechanism of Astragali Radix-Curcumae Rhizoma in treating gastric cancer based on network pharmacology and experimental verification

This study aims to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in the treatment of gastric cancer based on network pharmacology. Further, the SGC7901 cell model of gastric cancer was employed to validate the efficacy and key targets of the herb pair. Firstly, the CCK-8 assay was employed to evaluate the direct effect of HQEZ on the proliferation of gastric cancer SGC7901 cells. Then, network pharmacology methods were employed to investigate the active ingredients, key targets, and key signaling pathways involved in the treatment of gastric cancer with HQEZ. The results showed that HQEZ contained 18 potential active ingredients, such as quercetin, naringenin, and curcumin. The results of gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment suggested that the main targets of HQEZ in treating gastric cancer were involved in the regulation of protein serine/threonine kinase activity, activation of mitogen-activated protein kinase(MAPK) activity, cysteine-type endopeptidase activity, and negative regulation of protein serine/threonine kinase activity. The hypoxia-inducible factor-1(HIF-1) signaling pathway, ATP-binding cassette(ABC) transporters, cytochrome P450-mediated metabolism of xenobiotics, p53 signaling pathway, and cell apoptosis were key signaling pathways of HQEZ in treating gastric cancer. The cell experiments demonstrated that HQEZ significantly downregulated the expression of ATP-binding cassette subfamily B member 1(ABCB1), epidermal growth factor receptor(EGFR), phosphorylated serine/threonine kinase(p-AKT), hypoxia inducible factor 1 subunit alpha(HIF1A), B-cell lymphoma 2(BCL2), breast cancer susceptibility protein 1(BRCA1), DNA polymerase theta(POLH), ribonucleotide reductase M1(RRM1), and excision repair cross-complementation group 1(ERCC1), and upregulated the expression of tumor protein P53(TP53) and cysteinyl aspartate-specific proteinase(CAPS3). Finally, a multivariate COX regression model was adopted to study the relationship between gene expression and clinical information data of gastric cancer patients in the TCGA database, which demonstrated that the key targets of HQEZ were associated with the poor prognosis in gastric cancer patients. Further feature selection using the LASSO algorithm showed that EGFR, HIF1A, TP53, POLH, RRM1, and ERCC1 were closely associated with the survival of gastric can-cer patients. In conclusion, HQEZ regulates the expression of genes involved in DNA repair, survival, and apoptosis in gastric cancer cells via multiple targets and pathways, assisting the treatment of gastric cancer.

The Relationship between Single Nucleotide Polymorphism of ERCC1 Gene and the Response to Platinum Based Chemotherapy in Egyptian Non-Small Cell Lung Cancer Patients

Abstract Background Lung cancer (LC) is the second most common cancer diagnosed in both males and females. There are two subtypes of LC. Non-small cell lung cancer (NSCLC) is the major one. Treatment options for NSCLC depends mainly on the stage at diagnosis. The majority of the patients are diagnosed at advanced stages at time of presentation. Therefore, chemotherapy and radiotherapy play the dominant role in treatment of advanced NSCLC. The most commonly used chemotherapy is platinum-based chemotherapy as cisplatin and carboplatin and third generation drugs as vinorelbine and gemcitabine. The efficacy of platinum-based chemotherapy is limited by chemoresistance. The excision repair cross complementation group 1(ERCC1) gene is a member of nucleotide excision repair pathway that plays a critical role in the DNA repair by removing DNA covalent helix-distorting adducts. Aim of the Work In this study investigated the relationship between single nucleotide polymorphism of ERCC1 rs11615 and the response to platinum-based chemotherapy in Egyptian NSCLC patients in order to prevent the non-necessary exposure to the toxic effect of chemotherapy. Patients and Methods This is a cross-sectional study conducted on 50 NSCLC patients who were recruited from the Oncology Clinic in Ain Shams University Hospitals; twenty of them were responders to platinumbased chemotherapy and the other 30 were non-responders according to RECIST criteria. All subjects underwent full medical history focusing on tobacco smoking and family history of cancers, thorough clinical examination, histological diagnosis of NSCLC and TNM classification, radiological studies: computed tomography of chest and abdomen and laboratory investigations in the form of: complete blood picture (CBC), liver function tests and kidney function tests. Detection of the ERCC1 (T/C) polymorphism by realtime PCR was done for both the responders' and the non-responders' groups. Results There was no significant statistical difference observed between the responders’ and nonresponders’ groups regarding the genotype frequencies nor the allelic frequency (p &amp;gt; 0.05). Conclusion The present study did not confirm the presence of significant association between the genotypic frequencies nor the allelic frequencies of the ERCC1 rs 11615 among the responders' and the non-responders' groups. Further studies with higher sample size are needed to clarify the association.

Effect of ERCC1 polymorphisms on the response to platinum-based chemotherapy: A systematic review and meta-analysis based on Asian population.

Platinum-based chemotherapy is one of the most common treatments for many cancers; however, the effect of chemotherapy varies from individual to individual. Excision repair cross complementation group 1 (ERCC1) is widely recognized as a key gene regulating nucleotide excision repair (NER) and is closely associated with platinum response. Many studies have yielded conflicting results regarding whether ERCC1 polymorphisms can affect the response to platinum and overall survival (OS). Therefore, it is necessary to perform a meta-analysis of patients with specific races and cancer types. Eight databases (EMBASE, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, Scopus, VIP, China Biology Medicine disc and Wanfang databases) were searched. Results were expressed in terms of odds ratios (ORs), hazard ratios (HRs) and 95% CIs. In this study, rs11615, rs2298881 and rs3212986 SNPs were studied. In the comparison between CT and TT on the response to platinum, esophageal cancer [I2 = 0%, OR = 6.18, 95% CI(1.89,20.23), P = 0.003] and ovarian cancer [I2 = 0%, OR = 4.94, 95% CI(2.21,11.04), P<0.001] showed that the rs11615 CT genotype predicted a better response. In the comparison between CC and TT, ovarian cancer [I2 = 48.0%, OR = 6.15, 95% CI (2.56,14.29), P<0.001] indicated that the CC genotype predicted a better response. In the meta-analysis of OS, the CC genotype was related to longer OS than TT in ovarian cancer [TT vs CC: I2 = 57.7%, HR = 1.71, 95% CI (1.18, 2.49), P<0.001]. The ERCC1 rs11615 polymorphism was related to the response to platinum and OS, but the correlation is based on specific cancer types in the Asian population.

Association of ERCC1 and XPF polymorphisms with pediatric glioma susceptibility.

Association of ERCC1 and XPF polymorphisms with pediatric glioma susceptibility.

ERCC6 plays a promoting role in the progression of non-small cell lung cancer.

Although excision repair cross-complementing group 6 (ERCC6) has been reported to be associated with lung cancer risk, the specific roles of ERCC6 in non-small cell lung cancer (NSCLC) progression are inadequately studied. Thus, this study aimed to examine the potential functions of ERCC6 in NSCLC. The expression of ERCC6 in NSCLC was analyzed by immunohistochemical staining and quantitative PCR. Celigo cell count, colony formation, flow cytometry, wound-healing, and transwell assays were used to evaluate the effects of ERCC6 knockdown on the proliferation, apoptosis, and migration of NSCLC cells. The effect of ERCC6 knockdown on tumor-forming ability of NSCLC cells was estimated by establishing xenograft model. ERCC6 was highly expressed in NSCLC tumor tissues and cell lines, and high ERCC6 expression was significantly associated with poor overall survival. Additionally, ERCC6 knockdown significantly suppressed cell proliferation, colony formation and migration, while accelerated cell apoptosis of NSCLC cells in vitro. Moreover, ERCC6 knockdown inhibited tumor growth in vivo. Further studies verified that ERCC6 knockdown attenuated the expression levels of Bcl-w, CCND1, and c-Myc. Altogether, these data unveil a major role of ERCC6 in the progression of NSCLC, and ERCC6 is expected to become a novel therapeutic target for NSCLC treatment.

DNA repair in cardiomyocytes is critical for maintaining cardiac function in mice.

Heart failure has reached epidemic proportions in a progressively ageing population. The molecular mechanisms underlying heart failure remain elusive, but evidence indicates that DNA damage is enhanced in failing hearts. Here, we tested the hypothesis that endogenous DNA repair in cardiomyocytes is critical for maintaining normal cardiac function, so that perturbed repair of spontaneous DNA damage drives early onset of heart failure. To increase the burden of spontaneous DNA damage, we knocked out the DNA repair endonucleases xeroderma pigmentosum complementation group G (XPG) and excision repair cross-complementation group 1 (ERCC1), either systemically or cardiomyocyte-restricted, and studied the effects on cardiac function and structure. Loss of DNA repair permitted normal heart development but subsequently caused progressive deterioration of cardiac function, resulting in overt congestive heart failure and premature death within 6months. Cardiac biopsies revealed increased oxidative stress associated with increased fibrosis and apoptosis. Moreover, gene set enrichment analysis showed enrichment of pathways associated with impaired DNA repair and apoptosis, and identified TP53 as one of the top active upstream transcription regulators. In support of the observed cardiac phenotype in mutant mice, several genetic variants in the ERCC1 and XPG gene in human GWAS data were found to be associated with cardiac remodelling and dysfunction. In conclusion, unrepaired spontaneous DNA damage in differentiated cardiomyocytes drives early onset of cardiac failure. These observations implicate DNA damage as a potential novel therapeutic target and highlight systemic and cardiomyocyte-restricted DNA repair-deficient mouse mutants as bona fide models of heart failure.

ERCC6L facilitates the progression of laryngeal squamous cell carcinoma by the binding of FOXM1 and KIF4A

The role of excision repair cross-complementation group 6-like (ERCC6L) has been reported in several cancers, but little is known about its expression and function in laryngeal squamous cell carcinoma (LSCC). In this study, the expression of ERCC6L in LSCC was determined by immunohistochemistry and its correlation with prognostic factors was analyzed. Furthermore, cytological functional validation elucidated the role and underlying mechanisms of ERCC6L dysregulation in LSCC. Our data revealed that ERCC6L expression was elevated in LSCC and it’s correlated with TNM stage. In addition, ERCC6L knockdown LSCC cells showed decreased proliferation and migration, increased apoptosis, and reactive oxygen species (ROS). Mechanically, overexpression of ERCC6L promoted nuclear translocation of FOXM1 to facilitate direct binding to the KIF4A promoter and upregulated KIF4A expression. Furthermore, KIF4A knockdown attenuated the role of ERCC6L overexpression in promoting proliferation, migration, and tumorigenesis of LSCC cells. In summary, ERCC6L promoted the binding of FOXM1 and KIF4A in LSCC cells to drive their progression, which may be a promising target for precision therapy in this disease.

Perspectives of ERCC1 in early-stage and advanced cervical cancer: From experiments to clinical applications.

Cervical cancer is a public health problem of extensive clinical importance. Excision repair cross-complementation group 1 (ERCC1) was found to be a promising biomarker of cervical cancer over the years. At present, there is no relevant review article that summarizes such evidence. In this review, nineteen eligible studies were included for evaluation and data extraction. Based on the data from clinical and experimental studies, ERCC1 plays a key role in the progression of carcinoma of the uterine cervix and the therapeutic response of chemoradiotherapy. The majority of the included studies (13/19, 68%) suggested that ERCC1 played a pro-oncogenic role in both early-stage and advanced cervical cancer. High expression of ERCC1 was found to be associated with the poor survival rates of the patients. ERCC1 polymorphism analyses demonstrated that ERCC1 might be a useful tool for predicting the risk of cervical cancer and the treatment-related toxicities. Experimental studies indicated that the biological effects exerted by ERCC1 in cervical cancer might be mediated by its associated genes and affected signaling pathways (i.e., XPF, TUBB3, and. To move towards clinical applications by targeting ERCC1 in cervical cancer, more clinical, in-vitro, and in-vivo investigations are still warranted in the future.

Genetic Polymorphisms in ERCC1 Gene and Their Association with Response to Radiotherapy in Moroccan Patients with Nasopharyngeal Carcinoma.

Nasopharyngeal carcinoma (NPC) is a severe malignant disease. Despite its low frequency, NPC is very common in North African population. Radiotherapy is the standard therapeutic treatment of NPC. However, radioresistance hampers the success of treatment. At the molecular scale, radioresistance is due to genetic variations involved in DNA repair pathways in NPC patients. Several studies reported that single nucleotide polymorphisms (SNPs) in excision repair cross complementing group 1 (ERCC1) could be associated with radioresistance. In this optic, the present study aimed to evaluate the association between DNA repair gene polymorphisms ERCC1 C8092A and ERCC1 C118T and radiotherapy response of patients with NPC. A total of 95 patients with confirmed NPC were recruited at the Mohammed VI Center for Cancer Treatment, Casablanca - Morocco between 2016 and 2018. Two single nucleotide polymorphisms in ERCC1 gene were genotyped. Multiple analysis software was used to assess the correlation between these SNPs and radio-therapeutic response. Sequencing of ERCC1 C8092A polymorphism revealed that CC and CA genotypes were found in 51.6% and 45.3% of cases, respectively, whereas the homozygote AA genotype was reported in only 3.1% of cases. For ERCC1 C118T polymorphism, the heterozygote CT genotype was identified in 49.5% of cases. Homozygotes genotypes CC and TT were detected in 17.9% and 32.6% respectively of NPC cases. Of note, no significant association was found between the ERCC1 C8092A polymorphism and response to radiation therapy (p=0.81). Similarly, there was no significant association between the response to radiotherapy and allelic distribution (p=0.56). Likewise, no correlation was observed neither with genotypes (p=0.07) nor with alleles (p=0.09) of ERCC1 C118T polymorphism and response to radiation therapy. Our results clearly showed that ERCC1 C8092A and ERCC1 C118T polymorphisms were not associated with response to radiotherapy in Moroccan NPC patients. Large studies are warranted to confirm the role of these SNPs in therapeutic response of NPC patients.

The XRCC1 and TP53 gene polymorphisms are associated with advanced-stage disease and early distant metastasis at diagnosis in non-small cell lung cancer.

Studies on single nucleotide polymorphisms (SNPs) in non-small cell lung cancer (NSCLC) suggest that DNA repair capacity may have prognostic implications for disease recurrence and survival. However, there is no study investigating the relationship between SNPs and the risk of metastasis at the time of initial diagnosis in patients with NSCLC. This study aimed to investigate the potential predictive value of SNPs in detecting the risk of metastasis at the time of initial diagnosis and poor prognosis in patients with NSCLC. In this prospective cohort study, we evaluated 275 patients with NSCLC. Analysis of SNPs from peripheral blood cells was performed by a polymerase chain reaction. Excision repair cross-complementing group 1 (ERCC1)- Asn118Asn, excision repair cross-complementing group 2 (ERCC2)-Lys751Gln, X-ray repair cross-complementing group 1 (XRCC1)-Arg399Gln, and tumor protein 53 (TP53)-Arg72Pro polymorphisms were evaluated in conjunction with the development of metastasis. The ERCC1 normal genotype, ERCC2 heterozygote genotype, XRCC1 normal genotype, and TP53 normal genotype were associated with a higher stage and more advanced-stage disease at the time of initial diagnosis (P = 0.027, 0.005, <0.001, and 0.006, respectively). Also, XRCC1 normal genotype and TP53 normal genotype were associated with the risk of metastasis at the time of initial diagnosis (P = <0.001 and 0.002, respectively). Moreover, the XRCC1 normal genotype was associated with the risk of brain metastasis at the time of initial diagnosis (P = 0.031). We showed that SNPs are related to a higher stage and more advanced-stage disease at the time of initial diagnosis in patients with NSCLC, and XRCC1 and TP53 gene polymorphisms are associated with the risk of metastasis. These results may contribute to the identification of high-risk groups and may help to earlier diagnosis and treatment in patients with NSCLC.

Association between ERCC1 Gene Polymorphism (rs11615) and Colorectal Cancer Susceptibility: A Meta-Analysis of Medical Image Fusion and Safety Applications.

Colorectal cancer (CRC) is a malignant tumor of the colorectal mucosa epithelial tissue transformed. The fusion of data for medical imaging has become a central issue in such biomedical applications as image-guided surgery and radiotherapy. Currently, CRC has been one of the most threatening tumors affecting people's health worldwide. The excision repair cross-complementation group 1 (ERCC1) is a key enzyme for nucleotide excision repair (NER). Emerging epidemiological studies have indicated that the presence of colorectal cancer (CRC) may be relevant to the ERCC1 rs11615 genetic polymorphism. However, the results of ERCC1 rs11615 on CRC in these studies are controversial. We searched PubMed, Web of Science, Embase, CNKI, and CBM databases for the effects of ERCC1 rs11615 variant on CRC development. There was no meta-analysis focused on the diagnosis of colorectal cancer with ERCC1 rs11615 variant. We creatively carried out a meta-analysis of nine case-control studies and used Stata (version 12.0) software to integrate the pooled odds ratios (ORs) corresponding to a 95% confidence interval (CI) of overall and subgroup analysis. Our results suggest that a significant correlation was observed between rs11615 and the susceptibility of CRC OR 95% CI = 1.13 (1.04-1.23) under an allele genetic model and OR 95% CI = 1.14 (1.01-1.30) under a dominant genetic model for overall CRC. Significant statistical difference was also noted in Asians rather than Caucasians based on the ethnicity subgroups. These results suggested that there is a certain association between rs11615 and the susceptibility of colorectal cancer in the Asian populations.