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
Abstract
BACKGROUND

Colon cancer is acknowledged as one of the most common malignancies worldwide, ranking third in United States regarding incidence and mortality. Notably, approximately 40% of colon cancer cases harbor oncogenic KRAS mutations, resulting in the continuous activation of epidermal growth factor receptor signaling.

AIM

To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance.

METHODS

Weighted gene co-expression network analysis, in combination with additional bioinformatics analysis, were conducted to screen the key factors driving the progression of KRAS mutant colon cancer. Meanwhile, various in vitro experiments were also conducted to explore the biological function of transglutaminase 2 (TGM2).

RESULTS

Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival. Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer. Additionally, biological roles of the key gene TGM2 was also assessed, suggesting that the downregulation of TGM2 attenuated the proliferation, invasion, and migration of the KRAS mutant colon cancer cell line.

CONCLUSION

This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer. This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.

Keywords: Colon cancer, KRAS mutation, Transglutaminase 2, Weighted gene co-expression network analysis

Core Tip: In the present study, we aim to mine the pathogenic hub genes of KRAS mutant colon cancer via the multi-omics resources of public databases. We use a variety of bioinformatics methods to reveal core genes related to KRAS mutant colon cancer, and subsequently identify the core gene through colon cancer tissue array. Besides, our in vitro results demonstrate that small interfering RNA-induced transglutaminase 2 (TGM2) downregulation suppress the proliferation, migration and invasion of KRAS-mutated colon cell line, suggesting that TGM2 might be a therapeutic target for the treatment of colon cancer.