Identification of Common and Subtype-Specific Mutated Sub-Pathways for a Cancer

Haidan Yan; Xusheng Deng; Haifeng Chen; Jun Cheng; Jun He; Qingzhou Guan; Meifeng Li; Jiajing Xie; Jie Xia; Yunyan Gu; Zheng Guo

doi:10.3389/fgene.2019.01228

Identification of Common and Subtype-Specific Mutated Sub-Pathways for a Cancer

Front Genet. 2019 Nov 28:10:1228. doi: 10.3389/fgene.2019.01228. eCollection 2019.

Authors

Haidan Yan^{1

2}, Xusheng Deng^{1

2}, Haifeng Chen³, Jun Cheng^{1

2}, Jun He^{1

2}, Qingzhou Guan^{1

2}, Meifeng Li^{1

2}, Jiajing Xie^{1

2}, Jie Xia^{1

2}, Yunyan Gu⁴, Zheng Guo^{1

2}

Affiliations

¹ Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Department of Bioinformatics, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
² Key Laboratory of Medical Bioinformatics, Fujian Medical University, Fuzhou, China.
³ Department of General Surgery, Fuzhou Second Hospital Affiliated to Xiamen University, Xiamen, China.
⁴ Department of Systems Biology, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.

Abstract

The heterogeneity of cancer is a big obstacle for cancer diagnosis and treatment. Prioritizing combinations of driver genes that mutate in most patients of a specific cancer 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 identified 13 subtype-specific sub-pathways with at least 0.25 mutation frequency difference between LUAD and LSCC samples in Lung-data1, and 12 of the 13 sub-pathways were reproducible in Lung-data2 and Lung-data3. 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 candidates for cancer diagnoses and sub-pathway targeted treatments.

Keywords: cancer genes; common sub-pathways; drug targets; mutation; subtype-specific sub-pathways.