Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2024; 16(5): 2074-2090
Published online May 15, 2024. doi: 10.4251/wjgo.v16.i5.2074
Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis
Wei-Bin Peng, Yu-Ping Li, Yong Zeng, Kai Chen
Wei-Bin Peng, Yu-Ping Li, Yong Zeng, First People’s Hospital of Foshan, Foshan 528000, Guangdong Province, China
Kai Chen, Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515031, Guangdong Province, China
Author contributions: Peng WB and Li YP acquired and performed the bioinformatic analysis and wrote the original draft; Zeng Y helped the statistics of this work; Peng WB and Chen K carried out the lost-of-function experiments; Chen K designed this research and reviewed and edited the final manuscript; and all authors read and approved the final manuscript.
Supported by National Nature Science Foundation of China, No. 82100195; China Postdoctoral Science Foundation, No. 2021M700777; and Medical Research Project of Foshan Municipal Health Bureau, No. 20230349.
Institutional review board statement: All patients gave informed consent for participation, and the protocol for the study was approved by the ethics committee of the First People’s Hospital of Foshan (Approval No. FSYYY-EC-SOP-008-02.0-A09).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kai Chen, MD, Postdoc, Researcher, Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, No. 7 Raoping Road, Jinping District, Shantou 515031, Guangdong Province, China. chenkai89@126.com
Received: December 4, 2023
Peer-review started: December 4, 2023
First decision: January 23, 2024
Revised: February 4, 2024
Accepted: March 8, 2024
Article in press: March 8, 2024
Published online: May 15, 2024
ARTICLE HIGHLIGHTS
Research background

Colon cancer stands as one of the prevalent malignancies worldwide, ranking third in terms of both incidence and mortality in United States. Approximately 40% of colon cancer carry oncogenic KRAS mutations, which persistently activate the epidermal growth factor receptor signaling pathway.

Research motivation

In-depth analysis of the core pathogenic genes of KRAS mutant colorectal cancer is of great significance.

Research objectives

This study aims to clarify the pivotal molecules in patients with KRAS mutant colon cancer.

Research methods

The weighted gene co-expression network analysis and further bioinformatics analysis are conducted to screen the key KRAS mutation-driving factors using KRAS-mutated The Cancer Genome Atlas and Gene Expression Omnibus colon cancer cohort. Immunohistochemical assay on tissue array and lost-function experiments are used for further validation for the clinical relevance and biological function.

Research results

Integrated analysis demonstrated that transglutaminase 2 (TGM2) acted as an independent prognostic factor for progression-free survival of patients with KRAS mutant colon cancer. Immunohistochemical on tissue array reveals that TGM2 predicts a higher probability of perineural invasion in patients with KRAS mutant colon cancer. In vitro experiments demonstrated that the downregulation of TGM2 attenuated the proliferation, invasion, and migration of the KRAS mutant colon cancer cell line.

Research conclusions

TGM2 might play an important role in the progression of KRAS mutant colon cancer.

Research perspectives

This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer, providing a theoretical foundation for therapeutic approaches. Extensive clinical trials and fundamental research are required to substantiate our preliminary findings.