Prognostic value of hepatoma-derived growth factor-related protein 3 (HRP-3) methylation in non-small cell lung cancer

Lung cancer is the leading cause of cancer deaths worldwide and is usually associated with a late diagnosis and a poor prognosis. Transcriptional silencing by CpG island hypermethylation has become a critical component in the initiation and progression of lung cancer. Hepatoma-derived growth factor (HDGF) is a nuclear targeted mitogen to be a potent tumorigenic and prognostic factor in cancers. To examine the clinical impaction of HDGF-related protein 3 (HRP-3) in lung cancer, we determined its methylation status in resected samples of primary non-small cell lung cancer (NSCLC) and evaluated the association with clinicopathologic characteristics. HRP-3 methylation was found in 35.1 % NSCLCs (73/208), which was significantly higher than 8.6 % of adjacent normal tissues. However, no association between HRP-3 expression level and methylation was found. Significantly higher methylation was found in adenocarcinoma (AC) without EGFR mutation than in AC with EGFR mutation. Univariate analysis revealed that HRP-3 methylation was associated with increased survival in total patients and defined subgroups including men, ever-smokers, and squamous cell carcinoma patients. Our data indicate that HRP-3 methylation could potentially be used as tissue-based prognostic markers in NSCLC. Further studies with large numbers of patients are needed to confirm the clinical significance of HRP-3 methylation.