Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis

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.