Combined Effect of Metastasis-Related MicroRNA, miR-34 and miR-124 Family, Methylation on Prognosis of Non–Small-Cell Lung Cancer

Prognosis of lung cancer is very unfavorable due to late detection and metastasis. Methylation status of metastasis-related miR-34 and miR-124 genes was studied in 157 non–small-cell lung cancer patients. The worse effect of miR-34b/c and miR-124-3 methylation on prognosis could be combined. Background Many patients with non–small-cell lung cancer (NSCLC) still develop tumor metastasis and recurrence after pulmonary resection and are the primary causes of lung cancer treatment failure and death. MicroRNAs (miRs) have central roles during tumor metastasis and many miR genes are potentially subjected to control by DNA methylation in multiple tumor types. Recently, miR-34 and miR-124 have been demonstrated as potential regulators of the metastasis process in several cancer types. Materials and Methods We studied the methylation status of miR-34 and miR-124 families in 157 patients with NSCLC using methylation-specific polymerase chain reaction and evaluated the clinical effect of their methylation on the patients' prognosis. Results Methylation was detected in 30.6% for miR-34a, 40.8% for miR-34b/c, 30.6% for miR-124-1, 49.7% for miR-124-2, and 51.6% for miR-124-3 in NSCLC tissue. miR-34b/c methylation was significantly associated with age, gender, smoking status, histologic type, and pathologic stage. miR-34b/c, miR-124-2, and miR-124-3 methylation were significantly associated with worse survival in all patients (adjusted hazard ratio [HR_adj] for miR-34b/c, 3.34; 95% confidence interval [CI], 1.95-5.74; P < .0001; HR_adj for miR-124-2, 1.99; 95% CI, 1.19-3.32; P = .009; and HR_adj for miR-124-3, 2.10; 95% CI, 1.24-3.55; P = .006). When miR-34b/c and miR-124-3 methylation were combined, overall survival decreased as the number of methylations increased (P_trend < .0001). Conclusion These findings suggest that miR-34 and miR-124 loci methylation could be a tumor-associated frequent event during NSCLC tumorigenesis and could be used as powerful markers for the prognosis of patients with NSCLC.