LAPSE:2023.5866
Published Article
LAPSE:2023.5866
Comprehensive Analysis of Mutation-Based and Expressed Genes-Based Pathways in Head and Neck Squamous Cell Carcinoma
February 23, 2023
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.
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.
Record ID
Keywords
CBSJukebox, head and neck squamous cell carcinoma (HNSCC), pathway analysis, precision medicine
Subject
Suggested Citation
Keam B, Park JY, Kim JP, Kim GD, Yu YS, Cho SH, Kim S, Ahn HK, Chun SH, Kwon JH, Yun T, Kim JW, Kim JE, Ahn MJ, Kim JH, Yun HJ. Comprehensive Analysis of Mutation-Based and Expressed Genes-Based Pathways in Head and Neck Squamous Cell Carcinoma. (2023). LAPSE:2023.5866
Author Affiliations
Keam B: Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Korea [ORCID]
Park JY: Cbs Bioscience Inc., Daejeon-si 34036, Korea
Kim JP: Cbs Bioscience Inc., Daejeon-si 34036, Korea [ORCID]
Kim GD: Cbs Bioscience Inc., Daejeon-si 34036, Korea
Yu YS: Cbs Bioscience Inc., Daejeon-si 34036, Korea
Cho SH: Department of Hemato-Oncology, Chonnam National University Hwasun Hospital, Chonnam 58128, Korea
Kim S: Department of Biomedical Systems Informatics and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea [ORCID]
Ahn HK: Department of Medical Oncology, Gachon University Gil Medical Center, Incheon-si 21565, Korea
Chun SH: Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647, Korea [ORCID]
Kwon JH: Division of Hemato-Oncology, Department of Internal Medicine, Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Seoul 05355, Korea
Yun T: Rare Cancers Clinic, Center for Specific Organs Cancer, National Cancer Center, Goyang-si 10408, Korea
Kim JW: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea
Kim JE: Department of Pathology, Seoul National University College of Medicine, SMG-SNU Boramae Hospital, Seoul 07061, Korea [ORCID]
Ahn MJ: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
Kim JH: Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Korea
Yun HJ: Department of Internal Medicine, Chungnam National University Hospital, Daejeon-si 35015, Korea
Park JY: Cbs Bioscience Inc., Daejeon-si 34036, Korea
Kim JP: Cbs Bioscience Inc., Daejeon-si 34036, Korea [ORCID]
Kim GD: Cbs Bioscience Inc., Daejeon-si 34036, Korea
Yu YS: Cbs Bioscience Inc., Daejeon-si 34036, Korea
Cho SH: Department of Hemato-Oncology, Chonnam National University Hwasun Hospital, Chonnam 58128, Korea
Kim S: Department of Biomedical Systems Informatics and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea [ORCID]
Ahn HK: Department of Medical Oncology, Gachon University Gil Medical Center, Incheon-si 21565, Korea
Chun SH: Department of Internal Medicine, Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon 14647, Korea [ORCID]
Kwon JH: Division of Hemato-Oncology, Department of Internal Medicine, Hallym University College of Medicine, Kangdong Sacred Heart Hospital, Seoul 05355, Korea
Yun T: Rare Cancers Clinic, Center for Specific Organs Cancer, National Cancer Center, Goyang-si 10408, Korea
Kim JW: Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea
Kim JE: Department of Pathology, Seoul National University College of Medicine, SMG-SNU Boramae Hospital, Seoul 07061, Korea [ORCID]
Ahn MJ: Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea
Kim JH: Division of Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Korea
Yun HJ: Department of Internal Medicine, Chungnam National University Hospital, Daejeon-si 35015, Korea
Journal Name
Processes
Volume
9
Issue
5
First Page
792
Year
2021
Publication Date
2021-04-30
ISSN
2227-9717
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Original Submission
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PII: pr9050792, Publication Type: Journal Article
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LAPSE:2023.5866
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https://doi.org/10.3390/pr9050792
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Feb 23, 2023
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