J Cancer 2017; 8(6):1038-1044. doi:10.7150/jca.18169

Research Paper

Combined Detection of Plasma ZIC1, HOXD10 and RUNX3 Methylation is a Promising Strategy for Early Detection of Gastric Cancer and Precancerous Lesions

Zhenghua Lin1,2, Mengzhao Luo2,3, Xueqing Chen1, Xingkang He1,2, Yun Qian1,2, Sanchuan Lai1,2, Jianmin Si1,2✉, Shujie Chen1,2✉

1. Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, Zhejiang Province, China;
2. Institute of Gastroenterology, Zhejiang University, Hangzhou 310016, Zhejiang Province, China;
3. Department of Gastroenterology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China.

Abstract

We try to explore the value of aberrant DNA methylation of several cancer-related genes in plasma as non-invasive biomarkers for gastric cancer (GC) and precancerous lesions. By using methylation-specific polymerase chain reaction assay we determined the methylation status of three selected genes ZIC1, HOXD10 and RUNX3 in blood samples from patients with GC and precancerous lesions. We discovered that the methylation rate of ZIC1, HOXD10 and RUNX3 increased significantly in the progression of gastric carcinogenesis. Methylation of ZIC1 was associated with positive serum CA19-9, while that of HOXD10 was related to H. pylori status, serum CA19-9 and CEA levels and tumor invasion depth. The Odds ratios (ORs) of ZIC1, HOXD10 and RUNX3 methylation for predicting GC were 4.285 (95%CI: 2.435-7.542), 3.133 (95%CI: 1.700-5.775) and 2.674 (95%CI: 1.441-4.960), while for predicting “gastric cancer and intraepithelial neoplasia” (GnI), the ORs were 12.011 (95%CI: 0.050-28.564), 9.174 (95%CI: 3.220-26.135) and 12.794 (95%CI: 4.115-39.778), respectively. In terms of combined detection of these three genes, the sensitivity was 91.6% for GC and 89.8% for GnI, with the highest Youden index in both GC and GnI determination. Conclusively, combined detection of ZIC1, HOXD10 and RUNX3 promoter hypermethylation might be a promising strategy for early detection of GC and precancerous lesions.

Keywords: Gastric cancer, Zinc finger of the cerebellum 1, Homeobox D10, Runt-related transcription factor 3, DNA methylation

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How to cite this article:
Lin Z, Luo M, Chen X, He X, Qian Y, Lai S, Si J, Chen S. Combined Detection of Plasma ZIC1, HOXD10 and RUNX3 Methylation is a Promising Strategy for Early Detection of Gastric Cancer and Precancerous Lesions. J Cancer 2017; 8(6):1038-1044. doi:10.7150/jca.18169. Available from http://www.jcancer.org/v08p1038.htm