Prognostic value of let-7 in lung cancer: systematic review and meta-analysis

BACKGROUND: Lung cancer is the leading cause of cancer-related deaths worldwide and the overall survival of patients with non-small cell lung cancer has not been improved. Let-7 family has been shown to act as tumor suppressors by inhibiting oncogenes and key regulators of mitogenic pathways, while far fewer clinical studies addressing the association between let-7 expression and the disease prognosis have been published up to date. Therefore, our meta-analysis aims to determine the prognostic significance of let-7 expression in lung cancer patients. METHODS: PubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literature citations. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I2 statistic were used to estimate the level of heterogeneity. The publication bias was detected by Begg’s test and Egger’s test. RESULTS: Seven eligible studies involving 2,262 patients were selected for this meta-analysis. The combined HR for the seven eligible studies was 0.61 (95% CI: 0.53–0.70, P<0.00001) and heterogeneity of overall prognosis was relatively high (I(2)=76.4%, P=0.000). We conducted a further subgroup analysis, including an evaluation of the relationship between let-7 expression, lung cancer pathology, race, and sample size. All the results revealed that a significantly low let-7 expression in patients was an indicator of poor survival. Neither Begg’s test nor Egger’s test found publication bias in any analysis. CONCLUSIONS: The present evidence indicates that the low let-7 expression can be considered as a significant predictor of worse prognosis in patients with lung cancer. The findings of our meta-analysis may be further confirmed in the future by the use of more updated review pooling and more relevant investigations.