In-silico investigation reveals microbial metabolic biomarkers and their regulatory roles in hormone sensitive cancers

Abstract

Cancer burden has become a global concern, specifically with hormone-sensitive cancers (HSC). Among the various factors influencing the progress and treatment of cancers, the human microbiota plays a vital role. The current analysis explores the role of microbial metabolites in various regulatory pathways associated with cancer biomarkers and finds the common microbial metabolites associated with HSCs. AR, ESR1, and TP53 in breast cancer; ERBB2, MAPK21, and TP53 in ovarian cancer; AKT1, EGFR, and ERBB2 in endometrial cancer and AR, MYC, and RB1 in prostate cancer were identified as important genes in HSC development. The associated metabolites of these genes were contributing to various regulatory pathways. The metabolites hydrogen peroxide, adenosine triphosphate, adenosine diphosphate, guanosine diphosphate, and guanosine triphosphate produced by microbes within the humans were found to be involved in nucleotide and amino acid metabolism pathways. The purine and pyrimidine metabolism pathways, glyoxylate, and dicarboxylate metabolism pathway, arginine and proline pathway, and glycine, serine, and threonine pathways were found common and significantly enriched between human and microbial metabolites showing close association between the microbial metabolites and the HSCs. The microbes belonging to Bacteroidetes, Proteobacteria, and Firmicutes phylum were found to be significantly associated with HSCs. The expression analysis and the similar pathways enriched between the correlated genes and hub genes validated the significance of the metabolites which can be used as potential biomarkers. Thus, the metabolic biomarkers can help in early diagnosis, targeted therapy based on the microbiome, and in prevention of cancer.

Keywords

• Microbiome
• Nucleotide metabolism
• Metabolic pathways
• Metabolic biomarker
• Enrichment analysis