Combining methylated SEPTIN9 and RNF180 plasma markers for diagnosis and early detection of gastric cancer

作者：Yongzhan Nie, Xianchun Gao, Xiqiang Cai, Zhen Wu, Qiaoyi Liang, Guobing Xu, Na Liu, Peng Gao, Jingyu Deng, Hongzhi Xu, Zhanlong Shen, Chang-qi Cao, Fenrong Chen, Nannan Zhang, Yongxi Song, Mingjun Sun, Chengyin Liu, Zhou Guangpeng, Weili Han, Jianhua Dou, Huahong Xie, Liping Yao, Zhiguo Liu, Gang Ji, Xin Wang, Qingchuan Zhao, Lei Shang, Daiming Fan, Xiaoliang Han, Jianlin Ren, Han Liang, Zhenning Wang, Jinhai Wang, Qi Wu, Jun Yu, Kaichun Wu, the MAGIS Study Group · 发表于：癌症：英文版 · 年份：2023 · DOI：10.1002/cac2.12478 · 被引用次数：38 · 研究领域：Epigenetics and DNA Methylation、Cancer-related gene regulation、Gastric Cancer Management and Outcomes

Dear Editor, Early diagnosis is critical for successful treatment of gastric adenocarcinoma (GA). However, the sensitivities of tumor markers carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9) and CA72-4 for GA detection are approximately 20% [1], and the sensitivities of all markers combined for early gastric cancer detection is still very low [2]. DNA methylation plays a major role in tumorigenesis and therefore has obvious potential as a non-invasive biomarker for cancer detection [3]. Through genome-wide methylation analysis and histological verification, we previously identified ring finger protein 180 (RNF180) as a novel preferentially methylated gene in GA [4, 5]. To increase the sensitivity for detecting GA, we combined mRNF180 and other methylated DNA markers. According to previous studies, the sensitivity and specificity of circulating methylated SEPTIN9 (mSEPT9) are estimated to be 50%-70% and ≥ 90%, respectively, to detect colorectal cancer (CRC) [6, 7]. GA and CRC share similar biological features. Notably, GA and CRC share many similar aberrant promoter DNA methylations, resulting in sharing many consistent gene methylation biomarkers [8]. Therefore, we attempted to establish a panel of mRNF180 and mSEPT9 (RS9 panel) for the early detection of GA. The study protocols are included in the Supplementary Materials. To assess the diagnostic potential of the RS9 panel, we prospectively examined 324 plasma specimens from 195 GA patients and 129 controls in th...