Association between BIM deletion polymorphism and clinical outcome of EGFR-mutated NSCLC patient with EGFR-TKI therapy: A meta-analysis.

AIM: BIM deletion polymorphism was deemed to be associated with downregulation of BIM, resulting in a decreased apoptosis induced by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC). However, accumulating evidences concerning the association between BIM deletion polymorphism and efficacy of EGFR-TKI and survival in EGFR-mutation-driven NSCLC patient reported contradictory results. MATERIALS AND METHODS: A meta-analysis was conducted by combing six original eligible studies including 871 NSCLC patients. RESULTS: Our study showed that BIM deletion polymorphism was significantly associated with poor response to EGFR-TKI therapy in mutant EGFRNSCLC patients (P(h) = 0.309, P(z) = 0.001, OR = 0.39, 95% confidence interval (CI) = 0.23-0.67). Disease control rate (DCR) in mutant EGFRNSCLC patient with treatment of EGFR-TKI was significantly decreased in patients with BIM deletion polymorphism comparing to patients harbored BIM wild variant (P(h) = 0.583, P(Z) = 0.007, OR = 0.46, 95%CI = 0.25-0.85). EGFR mutation-derived NSCLC patient carrying BIM deletion polymorphism had a shorter progression-free survival (PFS; P(h) < 0.001, P(z) < 0.001, hazard ratio (HR) = 1.37, 95%CI = 1.09-1.71) and overall survival (OS; P(h) = 0.90, P(z) = 0.003, HR = 1.25, 95%CI = 1.08-1.45), than those harbored BIM wild variant. CONCLUSION: These results suggested that BIM deletion polymorphism might be a cause that contributes to primary EGFR-TKI resistance, and it could be used as a genetic predictor for EGFR-TKI outcome and an independent prognostic factor of EGFR mutation-driven NSCLC patient.

Rs895819 within miR-27a might be involved in development of non small cell lung cancer in the Chinese Han population.

MicroRNA-27a (miR-27a) is deemed to be an oncogene that plays an important role in development of various cancers, and single nucleotide polymorphism (SNP) of miR-27a can influence the maturation or aberrant expression of hsa-miR27a, resulting in increased risk of cancer and poor prognosis for non-small cell lung cancer (NSCLC). This study aimed to assess the effects of rs895819 within miR-27a on susceptibility and prognosis of NSCLC patients in 560 clinical confirmed cases and 568 healthy check-up individuals. Adjusted odds/hazard ratios (ORs/HRs) and 95% confidential intervals (CIs) were calculated to evaluate the association between rs895819 and the risk and prognosis of NSCLC. The results showed that allele A and genotype GG of rs895819 were significantly associated with an increased risk of NSCLC (38.9% vs 30.8%, adjusted OR=1.26, 95%CI=1.23-1.29 for allele G vs A; 18.1% vs 11.7%, adjusted OR=1.67, 95%CI=1.59-1.75 for genotype GG vs AA). Moreover, positive associations were also observed in dominant and recessive models (53.7% vs 49.9%, adjusted OR=1.17, 95%CI=1.13-1.20 for GG/AG vs AA; 18.1% vs 11.7%, adjusted=1.65, 95%CI=1.58-1.73). However, no significant association was found between rs895819 and the prognosis of NSCLC in genotype, dominant and recessive models. These results suggested that miR-27a might be involved in NSCLC carcinogenesis, but not in progression of NSCLC. The allele G, genotype GG and allele G carrier (GG/AG vs AA) of rs895819 might be genetic susceptible factors for NSCLC. Further multi-central, large sample size and well-designed prospective studies as well as functional studies are warranted to verify our findings.

Expression and significance of circulating microRNA-31 in lung cancer patients.

BACKGROUND: The aim of this study was to investigate the expression level of circulating microRNA-31(miRNA-31) in lung cancer patients and its clinical significance. MATERIAL AND METHODS: Real-time fluorescent quantitative PCR was utilized to detect the circulating miRNA-31 expression levels in 300 lung cancer patients and 300 health control subjects. The ROC curve was drawn to evaluate the diagnostic value of the circulating miRNA-31 expression levels in lung cancer. The 300 lung cancer patients were divided into a miRNA-31 low-expression group and a miRNA-31 high-expression group. A survival curve was drawn according to the Kaplan-Meier method to evaluate the prognostic value of the circulating microRNA-31 expression levels for lung cancer. RESULTS: The circulating miRNA-31 expression levels in the lung cancer patients (l.88±0. 67) increased significantly (P<0.001) compared to the healthy controls (0.58±0. 44). The area under the ROC curve drawn according to the circulating miRNA-31 expression levels was 0.785 (95% CI=0.486-0.763). When the critical value was 1.27, the sensitivity and specificity for lung cancer diagnosis according to the circulating miRNA-31 expression levels were 0.769 and 0.745, respectively. The difference in the survival curve between the miRNA-31 low-expression group (123 cases) and high-expression group (177 cases) was statistically significant (P=0.004). Median survival period of the low-expression group (38.44 months) was longer than that of the high-expression group (25.23 months). CONCLUSIONS: miRNA-31 may be a molecular marker for the diagnostic and prognostic evaluation of primary lung cancer.

Neuron specific enolase and prognosis of non-small cell lung cancer: a systematic review and meta-analysis.

PURPOSE: The predictive and prognostic role of neuron-specific enolase (NSE) in non-small cell lung cancer (NSCLC) is still under debate. The present meta-analysis aimed to evaluate the relation between serum NSE levels and the prognosis of NSCLC. METHODS: We performed a meta-analysis of published studies assessing the association of NSE with the prognosis of NSCLC. Literature retrieval, trials' selection and assessment, data collection, and statistical analysis were performed according to the Revman 5.0 guidelines. A fixed-effect model was used to pool the hazard ratio (HR) and 95% confidence intervals (95% CIs). RESULTS: A total of 8 eligible studies that included 2389 NSCLC patients were analyzed. We did not find prognostic value of NSE for NSCLC (HR=1.17, 95% CI: 0.95-1.44, p=0.14). CONCLUSION: The present study indicated that serum NSE level is of no prognostic significance in patients with NSCLC.