Genes Modulating Butyrate Metabolism for Assessing Clinical Prognosis and Responses to Systematic Therapies in Hepatocellular Carcinoma

Butyrate, one of the major products of the gut microbiota, has played notable roles in diverse therapies for multiple tumors. Our study aimed to determine the roles of genes that modulate butyrate metabolism (BM) in predicting the clinical prognosis and responses to systemic therapies in hepatocellular carcinoma (HCC). The genes modulating BM were available from the GeneCard database, and gene expression and clinical information were obtained from TCGA-LIHC, GEO, ICGC-JP, and CCLE databases. Candidate genes from these genes that regulate BM were then identified by univariate Cox analysis. According to candidate genes, the patients in TCGA were grouped into distinct subtypes. Moreover, BM- related gene signature (BMGs) was created via the LASSO Cox algorithm. The roles of BMGs in identifying high-risk patients of HCC, assessing the prognoses, and predicting systematic therapies were determined in various datasets. The statistical analyses were fulfilled with R 4.1.3, GraphPad Prism 8.0 and Perl 5.30.0.1 software. In the TCGA cohort, most butyrate-related genes were over-expressed in the B cluster, and patients in the B cluster showed worse prognoses. BMGs constructed by LASSO were composed of eight genes. BMGs exhibited a strong performance in evaluating the prognoses of HCC patients in various datasets, which may be superior to 33 published biomarkers. Furthermore, BMGs may contribute to the early surveillance of HCC, and BMGs could play active roles in assessing the effectiveness of immunotherapy, TACE, ablation therapy, and chemotherapeutic drugs for HCC. BMGs may be served as novel promising biomarkers for early identifying high-risk groups of HCC, as well as assessing prognoses, drug sensitivity, and the responses to immunotherapy, TACE, and ablation therapy in patients with HCC.