Affiliations: [a] College of Nursing, School of Medicine, Kyungpook National University, Daegu, Korea | [b] Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Korea | [c] Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
Correspondence:
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Corresponding authors: Jae Yong Park, Department of Internal Medicine, School of Medicine, Kyungpook National University, 2-101 Dongin-dong, Jung-gu, Daegu 702-422, Korea. Tel.: +82 53 420 5563; Fax: +82 53 427 1468; E-mail: [email protected]; Dong Sun Kim, Department of Anatomy, School of Medicine, Kyungpook National University, 2-101 Dongin-dong, Jung-gu, Daegu 702-422, Korea. Tel.: +82 53 420 4803; Fax: +82 53 427 1468; E-mail: [email protected].
Abstract: Dickkopf-1 (DKK1) is known as a negative regulator of the Wnt signaling pathway, which plays a crucial role in carcinogenesis. However, aberrant expression and the role of DKK1 in human cancers remain controversial. To estimate the role of DKK1 and its prognostic potential in lung cancer, promoter methylation of DKK1 was evaluated in 139 primary non-small cell lung cancers (NSCLCs) by methylation-specific PCR and its association with clinical and prognostic parameters. DKK1 hypermethylation was detected in 48.9% of neoplastic lung tissues and was significantly more frequent in stage I than the more advanced stages II-IIIA (P=0.04). Additionally, patients with DKK1 methylation had a better overall survival than those with no methylation under univariate analysis. When stratified by clinicopathologic features, DKK1 methylation was significantly associated with a favorable survival in a subset of patients. The current findings suggested that DKK1 promoter methylation may be a tumor-associated event in the early stage of NSCLC and could also be useful prognostic indicator for NSCLC. Further work may clarify the molecular basis of DKK1 action in progression of NSCLC.
