The predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in operable and advanced non-small-cell lung cancer

Objective: The incidence of brain metastases greatly varies in patients with non-small-cell lung cancer, and molecular markers are considered to predict brain metastases. Therefore, this study sought to identify the predictive value and potential mechanisms of miRNA-328 and miRNA-378 for brain metastases in non-small-cell lung cancer. Methods: Patients who received a curable surgery for their lung cancer were screened according to our criteria. Formalin-fixed paraffin-embedded samples from the patients were examined for the expression of miRNA-328 and miRNA-378 using real-time polymerase chain reaction and the expression of N-cadherin, E-cadherin, vascular endothelial growth factor, protein kinase C alpha and S100B were investigated using immunohistochemical staining. Results: In total, 86 patients were screened for this study and 23 patients were diagnosed with brain metastases during the follow-up period. Comparing patients with and without brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues were significantly different (P = 6.2 x 10(-5) and P = 2.8 x 10(-5), respectively). For the patients with brain metastases, the expression of miRNA-328 and miRNA-378 in tumor tissues compared with para-carcinoma tissues were also significantly different (P = 2.2 x 10(-5) and P = 1.6 x 10(-5), respectively). For patients with brain metastases, the association between miRNA-328 and protein kinase C alpha was significant (r = 0.591, P = 0.003), but that between miRNA-378 and protein kinase C alpha was not significant (r = 0.259, P = 0.232). Conclusions: The expression of miRNA-328 and miRNA-378 in tumor tissues can be used to predict brain metastases in patients with non-small-cell lung cancer. miRNA-328 might promote brain metastases by regulating the expression of protein kinase C alpha. However, the mechanisms of miRNA-378 to promote brain metastases should be studied in the future.