Oncotarget

Research Papers:

LINE-1 hypomethylation in normal colon mucosa is associated with poor survival in Chinese patients with sporadic colon cancer

Changhua Zhuo, Qingguo Li, Yuchen Wu, Yiwei Li, Jia Nie, Dawei Li, Junjie Peng, Peng Lian, Bin Li, Guoxiang Cai, Xinxiang Li and Sanjun Cai _

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Oncotarget. 2015; 6:23820-23836. https://doi.org/10.18632/oncotarget.4450

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Abstract

Changhua Zhuo1,2,*, Qingguo Li1,*, Yuchen Wu1, Yiwei Li1, Jia Nie3, Dawei Li1, Junjie Peng1, Peng Lian1, Bin Li3, Guoxiang Cai1, Xinxiang Li1, Sanjun Cai1

1Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China

2Department of Surgical Oncology, Fujian Provincial Cancer Hospital, Teaching Hospital of Fujian Medical University, Fuzhou 350014, People’s Republic of China

3Key Laboratory of Molecular Virology & Immunology, Unit of Molecular Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People’s Republic of China

*These authors have contributed equally to this work

Correspondence to:

Sanjun Cai, e-mail: [email protected]

Xinxiang Li, e-mail: [email protected]

Keywords: colon cancer, LINE-1, microsatellite instability, epigenetic modification, survival analysis

Received: March 06, 2015     Accepted: June 19, 2015     Published: June 29, 2015

ABSTRACT

Genetic and epigenetic pathways are not independent in colorectal cancer (CRC) carcinogenesis. We aimed to determine the influence of various molecular features on Chinese patients’ colon cancer-specific survival (CCSS). Various genetic and epigenetic modifications were detected in paired tumor and normal mucosa tissue samples. The prognostic variables regarding patient CCSS were determined. Overall, 127 patients, including 83 males and 44 females, completed a median follow-up of 65 (3–85) months. A mean LINE-1 methylation rate of 64.62% (range, 9.45–86.93) was observed. Hypermethylation at the hMLH1 gene promoter was detected in 26 (20.47%) patients. KRAS was mutated in 52 (40.94%) patients. Sixteen (12.60%) patients were confirmed as microsatellite instability (MSI)-High, and 76 (59.84%) were found to have loss of heterozygosity at 18q. The LINE-1 methylation level, MSI status, perineural invasion and distant metastases were confirmed as independent prognostic factors for patient CCSS. A stratified survival analysis further revealed that certain subgroups of patients with LINE-1 hypomethylation had significantly worse survival (all p < 0.05). Our data revealed that both genetic and epigenetic abnormalities can concurrently exist during colonic tumorigenesis. As a global epigenetic change, LINE-1 hypomethylation in normal colon mucosa might be associated with a worse outcome in certain Chinese patients with colon cancer.


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