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Epigenetic inactivation of Homeobox A5 gene in nonsmall cell lung cancer and its relationship with clinicopathological features
Author(s) -
Kim DongSun,
Kim MinJin,
Lee JiYun,
Lee SuMan,
Choi JunYoung,
Yoon GhilSuk,
Na YeonKyung,
Hong HaeSook,
Kim SangGeol,
Choi JinEun,
Lee ShinYeop,
Park JaeYong
Publication year - 2009
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20561
Subject(s) - biology , methylation , epigenetics , dna methylation , cancer research , lung cancer , cancer , homeobox , carcinogenesis , tumor suppressor gene , gene , gene expression , pathology , genetics , medicine
Promoter methylation is an important mechanism in gene silencing and is a key epigenetic event in cancer development. Homeobox A5 ( HOXA5 ) is a master regulator of the morphogenesis and cell differentiation to be implicated as a tumor suppressor gene in breast cancer, but its role in lung cancer is still unknown. In this study, we have investigated the methylation status of the promoter region of the HOXA5 gene in nonsmall cell lung cancers (NSCLCs) using nested and standard methylation‐specific PCR (MSP) and correlated the methylation status with clinicopathological features. With standard MSP analysis, HOXA5 methylation were found in 113 (81.3%) of 139 NSCLCs and 72 (51.8%) in their corresponding nonmalignant lung tissues. RT‐PCR and immunohistochemical analysis showed that HOXA5 methylation correlates with gene expression. Moreover, in the patients with stage I disease, HOXA5 methylation was more frequent in smokers than in never‐smokes ( P = 0.01). There was no influence of HOXA5 methylation on survival in all NSCLCs or at stages II–IV. However, in the patients with stage I disease, HOXA5 methylation was associated with a borderline significantly worse survival ( P = 0.09). These findings suggest that downregulation of the HOXA5 gene by aberrant promoter methylation occurs in the vast majority of NSCLCs and that it may play a role in the pathogenesis of NSCLC. Additional studies with larger sample sizes are required to evaluate the prognostic value of HOXA5 methylation in patients with stage I NSCLC. © 2009 Wiley‐Liss, Inc.