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Disease Markers
Volume 32, Issue 3, Pages 195-202
http://dx.doi.org/10.3233/DMA-2011-0877

Hypermethylated FAM5C and MYLK in Serum as Diagnosis and Pre-Warning Markers for Gastric Cancer

Lu Chen,1 Liping Su,1 Jianfang Li,1 Yanan Zheng,1 Beiqin Yu,1 Yingyan Yu,1 Min Yan,1 Qinlong Gu,1 Zhenggang Zhu,1 and Bingya Liu1

1Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2Department of Surgery, Shanghai Jiao Tong University School of Medicine, Shanghai, China

Received 23 February 2012; Accepted 23 February 2012

Copyright © 2012 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Most cases of gastric cancer (GC) are not diagnosed at early stage which can be curable, so it is necessary to identify effective biomarkers for its diagnosis and pre-warning. We have used methylated DNA immunoprecipitation (MeDIP) to identify genes that are frequently methylated in gastric cancer cell lines. Promoter regions hypermethylation of candidate genes were tested by methylation-specific polymerase chain reaction (MSP) in serum samples, including GC (n = 58), gastric precancerous lesions (GPL, n = 46), and normal controls (NC, n = 30). Eighty two hypermethylated genes were acquired by array analysis and 5 genes (BCAS4, CHRM2, FAM5C, PRAC and MYLK) were selected as the candidate genes. Three genes (CHRM2, FAM5C and MYLK) were further confirmed to show methylation rates increased with progression from NC to GPL, then to GC. There was obvious decrease in detection of FAM5C and MYLK hypermethylation, but not CHRM2, from preoperative to postoperative evaluation (P < 0.001). Combined detection of FAM5C and MYLK hypermethylation had a higher sensitivity in GC diagnosis (77.6%,45/58) and pre-warning (30.4%,14/46) than one single gene detection and also had a high specificity of 90%. The combined hypermethylated status of FAM5C and MYLK correlated with tumor size (P < 0.001), tumor invasion depth (P = 0.001) and tumor-node-metastasis (TNM) stage (P = 0.003). Hypermethylated FAM5C and MYLK can be used as potential biomarkers for diagnosis and pre-warning of GC.