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: 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 07/2014; 31(7):58. · 2.06 Impact Factor
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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: Clinical variables, like stage and performance status (PS), have predictive and prognostic values in advanced non-small cell lung cancer (NSCLC) patients treated with chemotherapy, not allowing adequate individual prediction. MicroRNA (miRNA) are non-coding RNAs regulating gene expression. In a prospective study, we assessed the predictive value for response and survival of tumour miRNA in NSCLC patients treated by 1st line cisplatin and vinorelbine. miRNA expression was analysed on a biopsy obtained during the diagnostic bronchoscopy, using TaqMan Low Density Arrays. The signature for response was derived using logistic regression with stepwise variable selection. The associations between overall survival and miRNA expression levels were estimated by using the Kaplan-Meier method, log-rank test, and Cox proportional hazard regression models to estimate the hazard ratios. In total, 38 patients with adequate tumour biopsies, treated with cisplatin-vinorelbine were included: male (n=27), 80-100 Karnofsky PS (n=27), adenocarcinoma (n=20), stage IV (n=30). One patient was considered not assessable for response but remained included in the survival analyses. Out of the 37 patients assessable for response, 16 partial responses (43%) were observed. A two miRNA signature (miR-149 and miR-375) was found predictive for response and was also associated to progression-free survival (p=0.05). Using a linear combination of the miR CT values with Cox's regression coefficients as weights, we constructed a prognostic score for overall survival including four miRNA (miR-200c, miR-424, miR-29c and miR-124). The signature distinguished patients with good (n=18) and poor (n=20) prognosis with respective median survival times of 47.3 months (95% CI 29.8-52.4) and 15.5 months (95% CI 9.1-22.8) (p<0.001; hazard ratio 21.1, 95% CI 4.7-94.9). miRNA signature allows predicting response and is of prognostic value for survival in patients with NSCLC treated with first line cisplatin and vinorelbine.Lung cancer (Amsterdam, Netherlands) 08/2013; · 3.14 Impact Factor