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

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 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.