Butyrate Metabolism-Related Gene Signature in Tumor Immune Microenvironment in Lung Adenocarcinoma: A Comprehensive Bioinformatics Study

Background

Experimental results have verified the suppressive impact of butyrate on tumor formation. Nevertheless, there is a limited understanding of the hidden function of butyrate metabolism within the tumor immune microenvironment (TIME) of lung adenocarcinoma (LUAD). This research aimed at digging the association between genes related to butyrate metabolism (butyrate metabolism-related genes [BMRGs) and immune infiltrates in LUAD patients.

Methods

Through analyzing The Cancer Genome Atlas dataset (TCGA), the identification of 38 differentially expressed BMRGs was made between LUAD and normal samples. Later, a prognostic signature made up of nine BMRGs was made to evaluate the risk score of LUAD subjects. Notably, high-risk scores emerged as negative prognostic indicators for overall survival in LUAD subjects. Additionally, BMRGs displayed associations with immunocyte infiltration levels, immune pathway activities, and pivotal prognostic hub BMRGs.

Results

One key prognostic BMRG, PTGDS, exhibited a robust correlation with T cells, the chemokine-related pathway, and the TCR signaling pathway. This study suggests that investigating the interplay between butyrate metabolism and T cells could present a promising novel approach to cancer treatment. OncoPredict analysis further unveiled distinct sensitivities of nine medicine in high- and low-risk groups, facilitating the selection of optimal treatment strategies for individual LUAD patients.

Conclusions

The study establishes that the BMRG signature serves as a sensitive predictive biomarker, providing profound insights into the crucial effect of butyrate metabolism in the context of LUAD TIME.