ERCC1 expression as a prognostic and predictive factor in patients with non-small cell lung cancer: a meta-analysis.
ABSTRACT It is hypothesized that high expression of the excision repair cross-complementation group 1 (ERCC1) gene might be a positive prognostic factor, but predict decreased sensitivity to platinum-based chemotherapy. Results from the published data are inconsistent. To derive a more precise estimation of the relationship between ERCC1 and the prognosis and predictive response to chemotherapy of non-small cell lung cancer (NSCLC), a meta-analysis was performed. An electronic search of the PubMed and Embase database was performed. Hazard ratio (HR) for overall survival (OS) was pooled in early stage patients received surgery alone to analyze the prognosis of ERCC1 on NSCLC. HRs for OS in patients received surgery plus adjuvant chemotherapy and in patients received palliative chemotherapy and relative risk (RR) for overall response to chemotherapy were aggregated to analyze the prediction of ERCC1 on NSCLC. The pooled HR indicated that high ERCC1 levels were associated with longer survival in early stage patients received surgery alone (HR, 0.69; 95% confidence interval (CI), 0.58-0.83; P = 0.000). There was no difference in survival between high and low ERCC1 levels in patients received surgery plus adjuvant chemotherapy (HR, 1.41; 95% CI, 0.93-2.12; P = 0.106). However, high ERCC1 levels were associated with shorter survival and lower response to chemotherapy in advanced NSCLC patients received palliative chemotherapy (HR, 1.75; 95% CI, 1.39-2.22; P = 0.000; RR, 0.77; 95% CI, 0.64-0.93; P = 0.007; respectively). The meta-analysis indicated that high ERCC1 expression might be a favourable prognostic and a drug resistance predictive factor for NSCLC.
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ABSTRACT: We analyzed the role of three common single-nucleotide polymorphisms (SNPs) of ERCC1 in predicting the tumor responses and the survival of non-small cell lung cancer (NSCLC) patients who received platinum-based chemotherapy. One hundred ninety-two patients who were identified as stage IV or IIIB/A NSCLC were collected between January 2008 and December 2009. ERCC1 rs11615, rs3212986, and rs2298881 were selected and genotyped by MassARRAY® Analyzer 4 system. One hundred three (53.65 %) patients showed a CR and PR to chemotherapy, and 81 (42.19 %) patients died from NSCLC with the median OS of 35.82 ± 15.19 months. Multivariate regression analysis showed that rs11615 TT genotype and T allele were associated with optimal response to chemotherapy, and rs3212986 AA and A allele were correlated with better response to chemotherapy. Cox regression showed that patients carrying the rs11615 TT genotype and T allele and the rs3212986 AA genotype and A allele were significantly associated with higher risk of death from NSCLC. In conclusion, ERCC1 rs11615 and rs3212986 polymorphism were associated with a poor response to chemotherapy and shorter survival time of advanced NSCLC. ERCC1 rs11615 and rs3212986 polymorphisms may be helpful for designing individualized cancer treatment for NSCLC patients.Tumor Biology 05/2014; · 2.84 Impact Factor
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ABSTRACT: The determination of in situ protein levels of ERCC1 with the 8F1 monoclonal antibody is prognostic of survival in patients with non-small cell lung cancer (NSCLC). The authors previously demonstrated that 8F1 recognizes a second nuclear antigen. This antigen was identified and its value as a biomarker of clinical outcomes analyzed. The second antigen was identified by mass spectrometry. Protein identity and antibody specificity were confirmed through knockdown and overexpression experiments. Immunohistochemistry of 187 early-stage NSCLC samples and 60 head and neck squamous cell carcinomas (HNSCCs) was used to examine the influence of the second antigen on 8F1 immunoreactivity and its association with patient outcomes. Choline phosphate cytidylyltransferase-α (CCTα, also known as phosphate cytidylyltransferase 1 choline alpha [PCYT1A], a phospholipid synthesis enzyme regulated by RAS) is the second antigen recognized by 8F1. In NSCLC samples, CCTα contributed (rho, 0.38) to 8F1 immunoreactivity. In samples of squamous cell carcinomas of the lung, CCTα was found to be the dominant determinant of 8F1 immunoreactivity, whereas its contribution in other subtypes of lung cancer was negligible. High expression of CCTα, but not ERCC1, was found to be prognostic of longer disease-free survival (log-rank P = .002) and overall survival (log-rank P = .056). Similarly, in patients with HNSCC, CCTα contributed strongly to 8F1 immunoreactivity (rho, 0.74), and high CCTα expression was found to be prognostic of survival (log-rank P = .022 for disease-free survival and P = .027 for overall survival). CCTα is the second antigen detected by 8F1. High CCTα expression appears to be prognostic of survival in patients with NSCLC who are treated by surgery alone and patients with HNSCC. CCTα is a promising biomarker of patient survival and deserves further study. Cancer. © 2014 American Cancer Society.Cancer 04/2014; · 5.20 Impact Factor
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ABSTRACT: Systemic therapy improves the survival and quality of life of patients with advanced stage non-small cell lung cancer (NSCLC). Several new therapeutic options have emerged for advanced NSCLC, incorporating novel cytotoxicity agents (taxanes, gemcitabine, pemetrexed) and molecular-targeted agents (erlotinib, bevacizumab) and the optimal prognostic marker for survival remains unclear. The aim of the present study was to assess the prognostic value of the clinicopathologic features and excision repair cross-complementation group-1 (ERCC1) in locally advanced NSCLC patients that received cisplatin-based chemotherapy. Clinical data concerning 80 patients with histopathologically confirmed non-small cell lung cancer who are planned to receive cisplatin-based adjuvant chemotherapy were collected. The protein expression levels for ERCC1 are immunohistochemical examined in 80 patients. The relationship between the ERCC1 protein expression level and the clinical outcomes of the patients is then observed. The 3-year survival rate and median survival time of stage III NSCLC received chemotherapy with/without concurrent chemoradiotherapy were 20 % and 10 months, respectively. Survival of patients with ERCC1-negative tumors was significantly longer than those with ERCC1-positive tumors (p = 0.0001). Prognostic factors with overall survival were performance status, cigarette smoking, stage, weight loss and ERCC1. While as regard progression-free survival prognostic factors were stage, weight loss, ERCC1 and degree of positivity of ERCC1 progression. It was found that ERCC1 protein expression might play an important role in the prognosis of locally advanced NSCLC patients treated with cisplatin-based adjuvant chemotherapy.Medical oncology (Northwood, London, England). 07/2014; 31(7):58.