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 (Northwood, London, England). 07/2014; 31(7):58.
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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: Exosomes are small extracellular membrane vesicles of endocytic origin released by many cells that could be found in most body fluids. The main functions of exosomes are cellular communication and cellular waste clean-up. This study was conducted to determine the involvement of exosomes in the regulation of sensitivity of the lung cancer cell line A549 to cisplatin (DDP). When DDP was added to A549 cells, exosomes secretion was strengthened. Addition of the secreted exosomes to other A549 cells increased the resistance of these A549 cells to DDP. Upon exposure of A549 to DDP, the expression levels of several miRNAs and mRNAs reportedly associated with DDP sensitivity changed significantly in exosomes; these changes may mediate the resistance of A549 cells to DDP. Exosomes released by A549 cells during DDP exposure decreased the sensitivity of other A549 cells to DDP, which may be mediated by miRNAs and mRNAs exchange by exosomes via cell-to-cell communication. Although the detailed mechanism of resistance remains unclear, we believed that inhibition of exosomes formation and release might present a novel strategy for lung cancer treatment in the future.PLoS ONE 01/2014; 9(2):e89534. · 3.53 Impact Factor