Serum microRNA-376 family as diagnostic and prognostic markers in human gliomas

BACKGROUND: MicroRNA (miR)-376 family play crucial roles in cancer formation and progression. OBJECTIVE: To investigate expression patterns of circulating miR-376 members in glioma patients, and to explore their diagnostic and prognostic values. METHODS: Expression of miR-376 members in serum samples from 100 glioma patients and 50 healthy controls were detected by quantitative real-time PCR. RESULTS: Serum miR-376a, miR-376b and miR-376c in glioma patients were significantly lower than those in healthy controls (all P < 0.05). Their expression could efficiently distinguish the glioma patients from healthy controls according to the receiver operating characteristic (ROC) analysis [for miR-376a, the area under ROC curve (AUC) = 0.872, the optimal cut-off value = 1.95, the sensitivity = 81.0% and the specificity = 82.0%; for miR-376b, AUC = 0.890, the optimal cut-off value = 2.07, the sensitivity = 82.0% and the specificity = 78.0%; for miR-376c, AUC = 0.837, the optimal cut-off value = 2.12, the sensitivity = 90.0% and the specificity = 70.0%; all P < 0.001]. Decreased expression of miR-376a, miR-376b and miR-376c in patients' sera were significantly associated with advanced WHO grade (all P < 0.01) and low KPS (all P < 0.05). Kaplan-Meier and Cox regression analyses showed that low miR-376a, miR-376b and miR-376c expression, and high grade were all independent factors predicting poor outcome of glioma patients. Notably, subgroup analyses showed that serum miR-376a, miR-376b and miR-376c levels had more significant prognostic values in patients with high grade gliomas than those with low grade gliomas. CONCLUSIONS: Aberrant expression of the miR-376 family may be involved into tumorigenesis and tumor progression of human gliomas. Circulating miR-376a, miR-376b and miR-376c may be promising non-invasive biomarkers for diagnosis and prognosis in glioma patients.