Genome-Wide Analysis Identified Three-Locus DNA Methylation Signature As Biomarkers with Superior Prediction Performance for Gastric Cancer Survival

Abstract

Background: The morbidity and mortality of gastric cancer (GC) is in the fourth and third place among all malignant tumors in the world. The prognosis is poor due to the lack of biomarkers for treatment selection. Methods: To select the methylation biomarkers related to overall survival of GC patients and improve the prognosis, we analyzed the methylation sequences of 388 GC patients from the Cancer Genome Atlas (TCGA) database. These patients were divided into training and testing datasets. Results: A total of 233 patients were randomly allocated to training dataset and 155 were allocated to testing dataset. The survival analysis showed that the three-DNA methylation signature was significantly correlated with overall survival of GC patients and could differentiate between high-risk and low-risk patients in training and testing datasets. Moreover, the three-DNA methylation signature could predict prognosis of GC patients with high sensitivity and specificity using receiver operating characteristic (ROC) analysis. The three-DNA methylation signature, independent of age, gender, radiation-therapy and histologic differentiation, could predict the prognosis of GC. It is noteworthy that the three-DNA methylation signature has higher prediction accuracy than the known biomarkers. Interpretation: Our results suggest that the three-DNA methylation signature was a useful prognostic indicator of GC and may have translational implications in GC clinical treatment. Funding Statement: This study was supported in part by grants from the National Natural Science Foundation of China (No. 31671311 and 81371033), the National first-class discipline program of Light Industry Technology and Engineering (LITE2018-14), the “Six Talent Peak” Plan of Jiangsu Province (No. SWYY-127), the Innovative and Entrepreneurial Talents of Jiangsu Province, the Program for High-Level Entrepreneurial and Innovative Talents Introduction of Jiangsu Province, Guangdong High-level Personnel of Special Support Program and Yangfan Plan of Talents Recruitment Grant, and Fundamental Research Funds for the Central Universities (JUSRP51712B and JUSRP1901XNC). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: Authors stated: Not applicable.