机构:[1]Hebei Med Univ, Hosp 4, Shijiazhuang, Hebei, Peoples R China河北医科大学第四医院[2]Beijing Univ Chinese Med, Sch Life Sci, Beijing, Peoples R China[3]China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing, Peoples R China[4]TCM Hosp Hebei Prov, Shijiazhuang, Hebei, Peoples R China[5]China Acad Chinese Med Sci, Inst Informat Tradit Chinese Med, Beijing, Peoples R China[6]Shanxi Buchang Pharmaceut Co Ltd, Xian, Shaanxi, Peoples R China
Several microRNAs (miRNAs) have been suggested as novel biomarkers for diagnosing gastric cancer (GC) at an early stage, but the single-marker strategy may ignore the co-regulatory relationships and lead to low diagnostic specificity. Thus, multi-target modular diagnostic biomarkers are urgently needed. In this study, a Z(summary) and NetSVM-based method was used to identify GC-related hub miRNAs and activated modules from clinical miRNA co-expression networks. The NetSVM-based sub-network consisting of the top 20 hub miRNAs reached a high sensitivity and specificity of 0.94 and 0.82. The Z(summary) algorithm identified an activated module (miR-486, miR-451, miR-185, and miR-600) which might serve as diagnostic biomarker of GC. Three members of this module were previously suggested as biomarkers of GC and its 24 target genes were significantly enriched in pathways directly related to cancer. The weighted diagnostic ROC AUC of this module was 0.838, and an optimized module unit (miR-451 and miR-185) obtained a higher value of 0.904, both of which were higher than that of individual miRNAs. These hub miRNAs and module have the potential to become robust biomarkers for early diagnosis of GC with further validations. Moreover, such modular analysis may offer valuable insights into multi-target approaches to cancer diagnosis and treatment.
基金:
National Major Scientific and Technological Special
Project for“Significant New Drugs
Development”(2017ZX09301059 to ZW), the
National Natural Science Foundation of China
(81673833 to JL, 81703947 to ZW) and The
Natural Science Foundation of Hebei province
(H2015206461 to FZ).
第一作者机构:[1]Hebei Med Univ, Hosp 4, Shijiazhuang, Hebei, Peoples R China
通讯作者:
通讯机构:[3]China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing, Peoples R China[5]China Acad Chinese Med Sci, Inst Informat Tradit Chinese Med, Beijing, Peoples R China[6]Shanxi Buchang Pharmaceut Co Ltd, Xian, Shaanxi, Peoples R China
推荐引用方式(GB/T 7714):
Zhang Fengbin,Xu Wenjuan,Liu Jun,et al.Optimizing miRNA-module diagnostic biomarkers of gastric carcinoma via integrated network analysis[J].PLOS ONE.2018,13(6):doi:10.1371/journal.pone.0198445.
APA:
Zhang, Fengbin,Xu, Wenjuan,Liu, Jun,Liu, Xiaoyan,Huo, Bingjie...&Wang, Zhong.(2018).Optimizing miRNA-module diagnostic biomarkers of gastric carcinoma via integrated network analysis.PLOS ONE,13,(6)
MLA:
Zhang, Fengbin,et al."Optimizing miRNA-module diagnostic biomarkers of gastric carcinoma via integrated network analysis".PLOS ONE 13..6(2018)