Clinical lung cancer, 2017, 01, e13─e20, DOI: https://doi.org/10.1016/j.cllc.2016.06.005

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

Young Hun Kim, Won Kee Lee; Eung Bae Lee; Ji Woong Son; Dong Sun Kim; Jae Yong Park

Abstract

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 nonesmall-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 nonesmall-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 [HRadj] for miR-34b/c, 3.34; 95% confidence interval [CI], 1.95-5.74; P < .0001; HRadj for miR-124-2, 1.99; 95% CI, 1.19-3.32; P ¼ .009; and HRadj for miR-124-3, 2.10; 95% CI, 1.24-3.55; P ¼ .006). When miR-34b/c and miR- 124-3 methylation were combined, overall survival decreased as the number of methylations increased (Ptrend < .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.

• DOI: https://doi.org/10.1016/j.cllc.2016.06.005
• ISBN or ISSN: 1525-7304

• 본 연구는 질병관리본부 연구개발과제(과제번호 2017-보건의료생물자원종합관리) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2017-보건의료생물자원종합관리) by Research of Korea Centers for Disease Control and Prevention.