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Comprehensive Analysis of Mutation-Based and Expressed Genes-Based Pathways in Head and Neck Squamous Cell Carcinoma

Authors
 Bhumsuk Keam  ;  Jin-Young Park  ;  Jin-Pyo Kim  ;  Gun-Do Kim  ;  Yun-Suk Yu  ;  Sang-Hee Cho  ;  Sangwoo Kim  ;  Hee-Kyung Ahn  ;  Sang-Hoon Chun  ;  Jung-Hye Kwon  ;  Tak Yun  ;  Ji-Won Kim  ;  Ji-Eun Kim  ;  Myung-Ju Ahn  ;  Joo-Hang Kim  ;  Hwan-Jung Yun 
Citation
 PROCESSES, Vol.9(5) : 792, 2021-04 
Journal Title
PROCESSES
Issue Date
2021-04
Keywords
head and neck squamous cell carcinoma (HNSCC) ; precision medicine ; pathway analysis ; CBSJukebox
Abstract
Over- or under-expression of mRNA results from genetic alterations. Comprehensive pathway analyses based on mRNA expression are as important as single gene level mutations. This study aimed to compare the mutation- and mRNA expression-based signaling pathways in head and neck squamous cell carcinoma (HNSCC) and to match these with potential drug or druggable pathways. Altogether, 93 recurrent/metastatic HNSCC patients were enrolled. We performed targeted gene sequencing using Illumina HiSeq-2500 for NGS, and nanostring nCounter® for mRNA expression; mRNA expression was classified into over- or under-expression groups based on the expression. We investigated mutational and nanostring data using the CBSJukebox® system, which is a big-data driven platform to analyze druggable pathways, genes, and protein-protein interaction. We calculated a Treatment Benefit Prediction Score (TBPS) to identify suitable drugs. By mapping the high score interaction genes to identify druggable pathways, we found highly related signaling pathways with mutations. Based on the mRNA expression and interaction gene scoring model, several pathways were found to be associated with over- and under-expression. Mutation-based pathways were associated with mRNA under-expressed genes-based pathways. These results suggest that HNSCCs are mainly caused by the loss-of-function mutations. TBPS found several matching drugs such as immune checkpoint inhibitors, EGFR inhibitors, and FGFR inhibitors
Files in This Item:
T202124656.pdf Download
DOI
10.3390/pr9050792
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biomedical Systems Informatics (의생명시스템정보학교실) > 1. Journal Papers
Yonsei Authors
Kim, Sangwoo(김상우) ORCID logo https://orcid.org/0000-0001-5356-0827
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/187390
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