
Am J Cancer Res 2012;2(1):116-129
Original Article
Prognostic significance of aberrant gene methylation in gastric cancer
Jing Shi, Guanjun Zhang, Demao Yao, Wei Liu, Na Wang, Meiju Ji, Nongyue He, Bingyin Shi, Peng Hou
Department of Endocrinology, The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine, Xi’an 710061, the
People’s Republic of China; Department of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University School of
Medicine, Xi’an 710061, the People’s Republic of China; Department of Surgery, The First Affiliated Hospital of Xi’an Jiaotong
University School of Medicine, Xi’an 710061, the People’s Republic of China; State Key Laboratory of Bioelectronics, Southeast
University, Nanjing 210096, the People’s Republic of China.
Received November 4, 2011; accepted November 19, 2011; Epub November 21, 2011; Published January 1, 2012
Abstract: Promoter methylation acts as an important alternative to genetic alterations for gene inactivation in gastric
carcinogenesis. Although a number of gastric cancer-associated genes have been found to be methylated in gastric cancer,
valuable methylation markers for early diagnosis and prognostic evaluation of this cancer remain largely unknown. In the present
study, we used methylation-specific PCR (MSP) to analyze promoter methylation of 9 gastric cancer-associated genes, including
MLF1, MGMT, p16, RASSF2, hMLH1, HAND1, HRASLS, TM, and FLNc, and their association with clinicopathological
characteristics and clinical outcome in a large cohort of gastric cancers. Our data showed that all of these genes were aberrantly
methylated in gastric cancer, ranging from 8% to 51%. Moreover, gene methylation was strongly associated with certain
clinicopathological characteristics, such as tumor differentiation, lymph node metastasis, and cancer-related death. Of interest,
methylation of MGMT, p16, RASSF2, hMLH1, HAND1, and FLNc was closely associated with poor survival in gastric cancer,
particularly MGMT, p16, RASSF2 and FLNc. Thus, our findings suggested these epigenetic events may contribute to the initiation
and progression of gastric cancer. Importantly, methylation of some genes were closely relevant to poor prognosis in gastric
cancer, providing the strong evidences that these hypermethylated genes may be served as valuable biomarkers for prognostic
evaluation in this cancer. (AJCR0000093).
Keywords: gastric cancer, gene methylation, methylation-specific PCR (MSP), early diagnosis, poor prognosis
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Address all correspondence to:
Peng Hou, Ph.D.
Department of Endocrinology
The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine,
Xi’an 710061, the People’s Republic of China
Tel/Fax: 86-298-532-4039
E-mail: phou@mail.xjtu.edu.cn
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