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Overall outcome of those patients with non-small cell lung cancer (NSCLC) remains poor. Recently, several studies demonstrated that cyclin-dependent kinase-5 (CDK5) activity with its specific activator protein p35 was important for spontaneous metastasis in various types of carcinomas. Our objective was to explore the expression of CDK5 and its prognostic indicator in patients with NSCLC. Immunofluorescent staining was used to detect the expression of CDK5/p35 in the lung tissue of 95 patients with NSCLC and 20 patients with benign pulmonary disease. The correlation between the expression of CDK5/p35 and clinicopathologic features of patients with NSCLC was investigated. The 5-year overall survival of patients with tumors expressing different levels of CDK5/p35 was evaluated by the Kaplan-Meier method. Positive expressions of CDK5/p35 were detected in the tumor cells in 66 samples (69.5%) of the 95 patients with NSCLC. Although no remarkable correlation between CDK5/p35 expression and age at the time of surgery, gender, and histopathologic type, there were significant differences between CDK5/p35 expression and degree of differentiation, pathological stage and lymph node metastasis in patients with NSCLC. In addition, we demonstrated that median survival for patients with and without CDK5/p35 expression was 24 and 58 months, respectively, and 5-year overall survival rate 25.8 and 48.3%, respectively (P<0.05). Patients with lung cancer with a positive CDK5/p35 expression had a poorer prognosis than those with a negative CDK5/p35 expression. Based on our results, CDK5/p35 may represent a biomarker for prognosis in patients with NSCLC.

BackgroundResistance to platinum-based chemotherapy remains a great challenge for ovarian cancer treatment. The human let-7 family contains 13 members located on nine different chromosomes, and most members have been implicated in the modulation of drug sensitivity in cancers. Our previous study showed that deregulation of let-7e in epithelial ovarian cancer (EOC) promoted the development of resistance to cisplatin. In the present study, we aimed to investigate the underlying mechanism and further evaluate the clinical value of let-7e in predicting chemo-response and prognosis in EOC.ResultsIn situ hybridization assays revealed a significantly decreased expression of let-7e in chemo-resistant EOC tissues compared with chemo-sensitive cases. Transfection with let-7e agomir sensitized EOC cells to cisplatin, down-regulated BRCA1 and Rad51 expression, and repressed the repair of cisplatin-induced DNA double strand break, while let-7e inhibitor exerted the opposite effects. In human EOC tissues, BRCA1 and Rad51 levels were increased in the chemo-resistant group compared with the sensitive group and were negatively correlated with let-7e. Low let-7e and high Rad51 were significantly associated with poor progression-free survival and overall survival and multivariate regression analyses showed that let-7e was an independent predictor for overall survival and chemotherapy response in EOC. Receiver operating characteristic analysis indicated that let-7e level was highly predictive of resistance to platinum-taxane chemotherapy with an area under the curve of 0.826.ConclusionsIn EOC, low let-7e leads to activation of BRCA1 and Rad51 expression and subsequent enhancement of DSB repair, which in turn results in cisplatin-resistance. Let-7e is a potential predictor for survival and chemo-response in EOC and re-expression of let-7e might be an effective strategy for overcoming chemo-resistance.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-017-0321-8) contains supplementary material, which is available to authorized users.