Bioinformatics and Experimental Analyses Reveal MAP4K4 as a Potential Marker for Gastric Cancer

Abstract

Background: Gastric cancer remains the most prevalent and highly lethal disease worldwide. MAP4K4, a member of Ste20, plays an important role in various pathologies, including cancer. However, its role in gastric cancer is not yet fully elucidated. Therefore, this study aims to determine the tumor-promoting role of MAP4K4 in gastric cancer and whether it can be used as a new and reliable biomarker to predict the prognosis of gastric cancer. For this purpose, we divide the samples into high- and low-expression groups according to the expression level of MAP4K4. The association of MAP4K4 expression with prognosis is assessed using the Kaplan–Meier survival analysis. Furthermore, immune infiltration analysis using ESTIMATE is conducted to evaluate the tumor immune scores of the samples. Results: The findings reveal a significantly higher expression of MAP4K4 in tumor samples than in adjacent samples. The high-expression group was significantly enriched in tumor-related pathways, such as the PI3K-Akt signaling pathway. In addition, immune infiltration analysis revealed a positive correlation between immune scores and MAP4K4 expression. We also observed that miRNAs, such as miR-192-3p (R = −0.317, p-value 3.111 × 10−9), miR-33b-5p (R= −0.238, p-value 1.166 × 10−5), and miR-582-3p (R = −0.214, p-value 8.430 × 10−5), had potential negative regulatory effects on MAP4K4. Moreover, we identified several transcription factors, ubiquitinated proteins, and interacting proteins that might regulate MAP4K4. The relationship between MAP4K4 and DNA methylation was also identified. Finally, we verified the high expression of MAP4K4 and its effect on promoting cancer. Conclusion: MAP4K4 might be closely related to gastric cancer’s progression, invasion, and metastasis. Its high expression negatively impacts the prognosis of gastric cancer patients. This suggests MAP4K4 as an important prognostic factor for gastric cancer and could be regarded as a new potential prognostic detection and therapeutic target.

Molecular Insights of MAP4K4 Signaling in Inflammatory and Malignant Diseases

“…Zhang et al reported overexpression of MAP4K4 kinase in gastric tumor samples. The overexpression of MAP4K4 was associated with gastric cancer’s invasion, progression, and metastasis, suggesting that MAP4K4 could serve as a prognostic marker for gastric cancer [ 77 ]. The regulatory role of MAP4K4 in GC cellular proliferation suggests that further in-depth study of MAP4K4 in GC is required to explore MAP4K4 as a therapeutic target.…”