miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis. The blood level of a microRNA, a small RNA molecule, predicts the outcome of chemotherapy in non-small cell lung cancer (NSCLC). MicroRNAs are non-coding RNAs that control the activity of specific genes. Hong Wang and Shi-yang Pan of Nanjing Medical University in China, and colleagues in China and USA, examined levels of the miR-638 microRNA in NSCLC cells in culture and also in mice and 200 human patients. When the cancers were treated with the drug cisplatin, increased miR-638 levels were found to accompany increased cancer cell death. Patients with higher miR-638 levels survived significantly longer than those with low levels, suggesting miR-638 could be a useful indicator of the likely success of chemotherapy. Examining the microRNA's effects may yield insights into the mechanisms of cancer and of effective chemotherapy.