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

IF 2.8 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Suvitha Anbarasu, Srujal Kacha, Sudha Ramaiah, Anand Anbarasu
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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.

计算机研究揭示了微生物代谢生物标志物及其在激素敏感性癌症中的调节作用。
癌症负担已成为全球关注的问题,特别是激素敏感性癌症(HSC)。在影响癌症进展和治疗的诸多因素中,人体微生物群起着至关重要的作用。目前的分析探讨了微生物代谢物在与癌症生物标志物相关的各种调节途径中的作用,并发现了与造血干细胞相关的常见微生物代谢物。乳腺癌中的AR、ESR1和TP53;ERBB2、MAPK21和TP53在卵巢癌中的作用子宫内膜癌中的AKT1、EGFR和ERBB2以及前列腺癌中的AR、MYC和RB1被确定为HSC发展的重要基因。这些基因的相关代谢物参与了各种调控途径。人体微生物产生的代谢产物过氧化氢、三磷酸腺苷、二磷酸腺苷、二磷酸鸟苷和三磷酸鸟苷参与了核苷酸和氨基酸的代谢途径。人体代谢产物与微生物代谢产物之间的嘌呤和嘧啶代谢途径、乙醛酸盐和二羧酸盐代谢途径、精氨酸和脯氨酸代谢途径以及甘氨酸、丝氨酸和苏氨酸代谢途径共同且显著富集,表明微生物代谢产物与造血干细胞密切相关。属于拟杆菌门、变形菌门和厚壁菌门的微生物被发现与造血干细胞显著相关。相关基因与枢纽基因之间的表达分析和富集的相似通路验证了代谢物的重要意义,可以作为潜在的生物标志物。因此,代谢生物标志物可以帮助早期诊断,基于微生物组的靶向治疗,以及预防癌症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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