Original Article
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 7, 2014; 20(29): 10071-10081
Published online Aug 7, 2014. doi: 10.3748/wjg.v20.i29.10071
KISS1 methylation and expression as predictors of disease progression in colorectal cancer patients
Shao-Qin Chen, Zhi-Hua Chen, Su-Yong Lin, Qi-Bao Dai, Leng-Xi Fu, Rui-Qing Chen
Shao-Qin Chen, Zhi-Hua Chen, Su-Yong Lin, Qi-Bao Dai, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Leng-Xi Fu, Rui-Qing Chen, Central Laboratory of Cancer Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, Fujian Province, China
Author contributions: All authors contributed equally to the work.
Supported by Natural Science Fund of Fujian Province, No. 2013-J01291; and National Key Construction Projects Clinical Specialties
Correspondence to: Shao-Qin Chen, MD, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Fujian Medical University, Chating Street, 20, Taijian, Fuzhou 350005, Fujian Province, China. chenshaoqin@medmail.com.cn
Telephone: +86-591-87982080 Fax: +86-591-87982082
Received: November 26, 2013
Revised: February 24, 2014
Accepted: March 4, 2014
Published online: August 7, 2014
Abstract

AIM: To examine the effect of aberrant methylation of the KISS1 promoter on the development of colorectal cancer (CRC) and to investigate reversing aberrant methylation of the KISS1 promoter as a potential therapeutic target.

METHODS: KISS1 promoter methylation, mRNA expression and protein expression were detected by methylation-specific polymerase chain reaction (PCR), real-time quantitative PCR and Western blotting, respectively, in 126 CRC tissues and 142 normal colorectal tissues. Human CRC cells with KISS1 promoter hypermethylation and poor KISS1 expression were treated in vitro with 5-aza-2’-deoxycytidine (5-Aza-CdR). After treatment, KISS1 promoter methylation, KISS1 mRNA and protein expression and cell migration and invasion were evaluated.

RESULTS: Hypermethylation of KISS1 occurred frequently in CRC samples (83.1%, 105/126), but was infrequent in normal colorectal tissues (6.34%, 9/142). Moreover, KISS1 methylation was associated with tumor differentiation, the depth of invasion, lymph node metastasis and distant metastasis (P < 0.001). KISS1 methylation was also associated with low KISS1 expression (P < 0.001). Furthermore, we observed re-expression of the KISS1 gene and decreased cell migration after 5-Aza-CdR treatment in a CRC cell line.

CONCLUSION: These data suggest that KISS1 is down-regulated in cancer tissues via promoter hypermethylation and therefore may represent a candidate target for treating metastatic CRC.

Keywords: Colorectal cancer, KISS1, Methylation, 5-aza-2’-deoxycytidine, Metastasis

Core tip:KISS1 promoter methylation and expression were measured in colorectal cancer (CRC) samples to determine the effect of aberrant methylation of the KISS1 promoter during the development of CRC. We determined that KISS1 hypermethylation occurred frequently in CRC and was associated with low KISS1 expression. KISS1 methylation was associated with tumor differentiation, the depth of invasion, lymph node metastasis and distant metastasis. We treated the human HCT116 colorectal carcinoma cell line, which exhibits KISS1 promoter hypermethylation and poor KISS1 expression, with 5-aza-2’-deoxycytidine in vitro. After treatment, we observed re-expression of the KISS1 gene and decreased cell migration.