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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01228

Identification of common and subtype-specific mutated sub-pathways for a cancer

 Haidan Yan1, Xusheng Deng1, Jun Cheng1, Jun He1, Qingzhou Guan1, Meifeng Li1, Jiajing Xie1, Jie Xia1,  Yunyan Gu2 and  Zheng Guo1*
  • 1School of Basic Medical Sciences, Fujian Medical University., China
  • 2Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China, China

The heterogeneity of cancer is a big obstacle for cancer diagnosis and treatment. Therefore, prioritizing combinations of driver genes that mutate in most patients of a specific cancer type or a subtype of this cancer is a promising way to tackle this problem. Here, we developed an empirical algorithm, named PathMG, to identify common and subtype-specific mutated sub-pathways for a cancer. By analyzing mutation data of 408 samples (Lung-data1) for lung cancer, three sub-pathways each covering at least 90% of samples were identified as the common sub-pathways of lung cancer. These sub-pathways were enriched with mutated cancer genes and drug targets and were validated in two independent datasets (Lung-data2 and Lung-data3). Especially, applying PathMG to analyze two major subtypes of lung cancer, lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LSCC), we found and validated six LUAD-specific sub-pathways and seven LSCC-specific sub-pathways. Two LUAD-specific and three LSCC-specific sub-pathways were significantly associated with the prognosis of lung cancer. Similar analyses were done for colorectal cancer. Together, PathMG provides us a novel tool to identify potential common and subtype-specific sub-pathways for a cancer, which can provide evidences for subtype diagnoses and pathway-targeted treatments.

Keywords: Mutation, common sub-pathways, subtype-specific sub-pathways, cancer genes, Drug Targets

Received: 04 Sep 2019; Accepted: 06 Nov 2019.

Copyright: © 2019 Yan, Deng, Cheng, He, Guan, Li, Xie, Xia, Gu and Guo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Zheng Guo, School of Basic Medical Sciences, Fujian Medical University., Fuzhou, China, guoz@ems.hrbmu.edu.cn