Journal
CANCER BIOLOGY & THERAPY
Volume 11, Issue 5, Pages 490-496Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.11.5.14550
Keywords
lung neoplasm; early stage; microRNA-34; hypermethylation; methylation-specific PCR; recurrence; prognosis
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Funding
- International Science and Technology Corporation
- Ministry of Science and Technology, China [2010DFB30650]
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Lung cancer is the leading cause of cancer-related death in the world and approximately 30-40% of patients with stage I non-small cell lung cancer (NSCLC) die of recurrent disease. miRNA expression profiles can be diagnostic and prognostic markers of lung cancer. Recently, miR-34 family has been shown to be part of the p53 pathway which is frequently involved in lung cancer, and the expression of miR-34 has been reported to be regulated by DNA methylation. In present study, we investigated the correlation between DNA methylation status of miR-34 family and recurrence of stage I NSCLC patients. miR-34a and miR-34b/c promoter methylation status were determined by nested methylation-specific PCR in FFPE tumor tissues from 161 patients of stage I NSCLC. Furthermore, mature miR-34b and miR-34c expression were analyzed by qRT-PCR in the same panel tissues. Our results revealed that aberrant DNA methylation of miR-34b/c was correlated with a high probability of recurrence (p = 0.026) and associated with poor overall survival (p = 0.010) and disease-free survival (p = 0.017). No significant association was found for miR-34a methylation. Multivariate analysis showed that promoter hypermethylation of miR-34b/c was an independent prognostic factor of stage I NSCLC. Moreover, no significant association between mature miR-34b and miR-34c expression and DNA methylation status was found. In conclusion, we have identified promoter hypermethylation of miR-34b/c as a relatively common event in NSCLC and might be a potential prognostic factor for stage I NSCLC.
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