ERCC1 expression as a prognostic and predictive factor in patients with non-small cell lung cancer: A meta-analysis

Department of Oncology, Huashan Hospital, Fudan University, Shanghai, China.
Molecular Biology Reports (Impact Factor: 2.02). 02/2012; 39(6):6933-42. DOI: 10.1007/s11033-012-1520-4
Source: PubMed


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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    • "As such, we supposed that some miRNAs and mRNAs reportedly associated with DDP resistance might be transferred from one cell to another by exosomes. MiR-21, miR-98, miR-133b, miR-138, miR-181a and miR-200c [19]–[24] were reportedly associated with DDP sensitivity regulation, whereas ERCC1, BRCA1 and RRM1 [25]–[27] were related to DDP resistance. To test our hypotheses, these miRNAs and mRNAs were selected to preliminarily study their involvement in the process of DDP resistance. "
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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 02/2014; 9(2):e89534. DOI:10.1371/journal.pone.0089534 · 3.23 Impact Factor
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    • "ERCC1 can recognize and remove these adducts and covalent cross-links, thus resistant to platinum agents [12]. A recent meta-analysis indicated that high ERCC1 level was a positive prognostic factor, being associated with shorter survival and lower response to platinum-based chemotherapy in advanced NSCLC patients [23]. Interestingly, we revealed that the SUVmax of ERCC1-positive cases were significantly higher than that of ERCC1-negative cases, there was statistical correlation between SUVmax and ERCC1 level, but failed to detect robust correlationship when the multiple stepwise regression was performed. "
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    ABSTRACT: The chemotherapy resistance of non-small cell lung cancer (NSCLC) remains a clinic challenge and is closely associated with several biomarkers including epidermal growth factor receptor (EGFR) ( Drugs 72(Suppl 1):28--36, 012.), p53 ( Med Sci Monit 11(6):HY11--HY20, 2005.) and excision repair cross complementing gene 1 (ERCC1) ( J Thorac Oncol 8(5):582--586, 2013.). Fluorodeoxyglucose positron emission tomography (FDG--PET) is the best non-invasive surrogate for tumor biology with the maximal standardized uptake values (SUVmax) being the most important paradigm. However, there are limited data correlating FDG-PET with the chemotherapy resistant tumor markers. The purpose of this study was to determine the correlation of chemotherapy related tumor marker expression with FDG--PET SUVmax in NSCLC. FDG--PET SUVmax was calculated in chemotherapy naive patients with NSCLC (n = 62) and immunohistochemical analysis was performed for EGFR, p53 or ERCC1 on the intraoperative NSCLC tissues. Each tumor marker was assessed independently by two pathologists using common grading criteria. The SUVmax difference based on the histologic characteristics, gender, differentiation, grading and age as well as correlation analysis among these parameters were performed. Multiple stepwise regression analysis was further performed to determine the primary predictor for SUVmax and the receiver operating characteristics (ROC) curve analysis was performed to detect the optimized sensitivity and specificity for SUVmax in suggesting chemotherapy resistant tumor markers. The significant tumor type (P = 0.045), differentiation (P = 0.021), p53 (P = 0.000) or ERCC1 (P = 0.033) positivity dependent differences of SUVmax values were observed. The tumor differentiation is significantly correlated with SUVmax (R = -0.327), tumor size (R = -0.286), grading (R = -0.499), gender (R = 0.286) as well as the expression levels for p53 (R = -0.605) and ERCC1 (R = -0.644). The expression level of p53 is significantly correlated with SUVmax (R = 0.508) and grading (R = 0.321). Furthermore, multiple stepwise regression analysis revealed that p53 expression was the primary predictor for SUVmax. When the cut-off value of SUVmax was set at 5.15 in the ROC curve analysis, the sensitivity and specificity of SUVmax in suggesting p53 positive NSCLC were 79.5% and 47.8%, respectively. The current study suggests that SUVmax of primary tumor on FDG-PET might be a simple and good non-invasive method for predicting p53-related chemotherapy resistance in NSCLC when we set the cu-off value of SUVmax at 5.15.
    BMC Cancer 11/2013; 13(1):546. DOI:10.1186/1471-2407-13-546 · 3.36 Impact Factor
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    • "It is possible that the presence of ERCC1 reflects an inherent biologic characteristic of the tumor. The ERCC1 expression level has recently been reported to be a prognostic factor in the survival of patients with early stage NSCLC [8,12]. Our study evaluated the effect of intratumoral ERCC1 expression on the survival of patients with completely resected p-stage III/N2 NSCLC. "
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    ABSTRACT: Background Pathological stage III/N2 non-small cell lung cancer (NSCLC) is heterogeneous, and the optimal prognostic marker for survival remains unclear in Chinese patients. The aim of the present study was to assess the prognostic value of the clinicopathologic features and excision repair cross-complementing group-1 (ERCC1) in resected p-stage III/N2 NSCLC patients that received cisplatin-based adjuvant chemotherapy. Methods Clinical data concerning 115 patients with histopathologically confirmed stage III/N2 NSCLC who underwent a complete resection were reviewed retrospectively. All patients received cisplatin-based adjuvant chemotherapy. The protein expression levels for ERCC1 were immunohistochemically examined in 115 patients. The relationship between the ERCC1 protein expression level and the clinical outcomes of the patients was then observed. Results The 5-year survival rate and median survival time of patients with pathological stage III/N2 NSCLC after surgery and postoperative chemotherapy was 27.0% and 28.0 months, respectively. Survival of patients with ERCC1 negative tumors was significantly longer than those with ERCC1 positive tumors (p = 0.004). However, it was not entirely clear whether adjuvant chemotherapy with cisplatin-based agents was beneficial for ERCC1-negative patients with p-stage III/N2. A multivariate analysis of survival in patients with stage III/N2 NSCLC showed that surgical procedure (pneumonectomy vs. lobectomy; p = 0.001), number of involved lymph nodes (≤5 vs. >5; p = 0.001) and ERCC1 protein expression (negative vs. positive; p = 0.012) were significant prognostic factors. In addition, the prognosis of patients with skip mediastinal lymph node metastasis showed a tendency for improved survival, but this was no significant (p = 0.432). Conclusions Findings from this retrospective study suggested that the number of involved lymph nodes and the type of pulmonary resection are significant and independent prognosis factors in patients with p-stage III/N2 NSCLC. In addition, it was found that ERCC1 protein expression might play an important role in the prognosis of p-stage III/N2 NSCLC patients treated with cisplatin-based adjuvant chemotherapy.
    Journal of Cardiothoracic Surgery 06/2013; 8(1):149. DOI:10.1186/1749-8090-8-149 · 1.03 Impact Factor
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