Using bioinformatics approaches to investigate driver genes and identify BCL7A as a prognostic gene in colorectal cancer

Jeffrey Yung-chuan Chao; Hsin-Chuan Chang; Jeng-Kai Jiang; Chih-Yung Yang; Fang-Hsin Chen; Yo-Liang Lai; Wen-Jen Lin; Chia-Yang Li; Shu-Chi Wang; Muh-Hwa Yang; Yu-Feng Lin; Wei-Chung Cheng

Computational and Structural Biotechnology Journal (Jan 2021)

Using bioinformatics approaches to investigate driver genes and identify BCL7A as a prognostic gene in colorectal cancer

Jeffrey Yung-chuan Chao,
Hsin-Chuan Chang,
Jeng-Kai Jiang,
Chih-Yung Yang,
Fang-Hsin Chen,
Yo-Liang Lai,
Wen-Jen Lin,
Chia-Yang Li,
Shu-Chi Wang,
Muh-Hwa Yang,
Yu-Feng Lin,
Wei-Chung Cheng

Affiliations

Jeffrey Yung-chuan Chao: Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan
Hsin-Chuan Chang: Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei, Taiwan
Jeng-Kai Jiang: Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan
Chih-Yung Yang: Department of Teaching and Research, Taipei City Hospital, Taipei, Taiwan; Commission for General Education, National United University, Miaoli, Taiwan; General Education Center, University of Taipei, Taipei, Taiwan
Fang-Hsin Chen: Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan; Department of Radiation Oncology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Institute for Radiological Research, Chang Gung University and Chang Gung Memorial Hospital, Taoyuan, Taiwan
Yo-Liang Lai: Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan
Wen-Jen Lin: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
Chia-Yang Li: Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Shu-Chi Wang: Division of Medical Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan
Muh-Hwa Yang: Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Division of Medical Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan
Yu-Feng Lin: Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan; Corresponding authors at: Graduate Institute of Biomedical Science, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung 406040, Taiwan (Wei-Chung Cheng); Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, No. 500, Lioufeng Rd., Wufeng, Taichung 41354, Taiwan (Yu-Feng Lin).
Wei-Chung Cheng: Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan; The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 404, Taiwan; Research Center for Cancer Biology, China Medical University, Taichung, Taiwan; Corresponding authors at: Graduate Institute of Biomedical Science, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung 406040, Taiwan (Wei-Chung Cheng); Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, No. 500, Lioufeng Rd., Wufeng, Taichung 41354, Taiwan (Yu-Feng Lin).

Journal volume & issue: Vol. 19
pp. 3922 – 3929

Abstract

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Colorectal cancer (CRC) results from the uncontrolled growth of cells in the colon, rectum, or appendix. The 5-year relative survival rate for patients with CRC is 65% and is correlated with the stage at diagnosis (being 91% for stage I at diagnosis versus 12% for stage IV). This study aimed to identify CRC driver genes to assist in the design of a cancer panel to detect gene mutations during clinical early-stage screening and identify genes for use in prognostic assessments and the evaluation of appropriate treatment options. First, we utilized bioinformatics approaches to analyze 354 paired sequencing profiles from The Cancer Genome Atlas (TCGA) to identify CRC driver genes and analyzed the sequencing profiles of 38 patients with >5 years of follow-up data to search for prognostic genes. The results revealed eight driver genes and ten prognostic genes. Next, the presence of the identified gene mutations was verified using tissue and blood samples from Taiwanese CRC patients. The results showed that the set identified gene mutations provide high coverage for driver gene screening, and APC, TP53, PIK3CA, and FAT4 could be detected in blood as ctDNA test targets. We further found that BCL7A gene mutation was correlated with prognosis in CRC (log-rank p-value = 0.02), and that mutations of BCL7A could be identified in ctDNA samples. These findings may be of value in clinical early cancer detection, disease monitoring, drug development, and treatment efforts in the future.

Published in Computational and Structural Biotechnology Journal

ISSN: 2001-0370 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Technology: Chemical technology: Biotechnology
Website: https://www.journals.elsevier.com/computational-and-structural-biotechnology-journal

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