Journal Article

Identifying distinctive tissue and fecal microbial signatures and the tumor-promoting effects of deoxycholic acid on breast cancer

Xu, Junnan, Han, Mengzhen, Yang, Jun, Liu, Xiaolin, Cao, Hui, Sun, Tao, Jiang, Lei, Jing, Mingxi, Wang, Na, Han, Wenjie

2022

Overview

A growing body of evidence indicates that the dysbiosis of both mammary and intestinal microbiota is associated with the initiation and progression of breast tumors. However, the microbial characteristics of patients with breast tumors vary widely across studies, and replicable biomarkers for early-stage breast tumor diagnosis remain elusive. We demonstrate a machine learning-based method for the analysis of breast tissue and gut microbial differences among patients with benign breast disease, patients with breast cancer (BC), and healthy individuals using 16S rRNA sequence data retrieved from eight studies. QIIME 2.0 and R software (version 3.6.1) were used for consistent processing. A naive Bayes classifier was trained on the RDP v16 reference database to assign taxonomy using the Vsearch software. After re-analyzing with a total of 768 breast tissue samples and 1,311 fecal samples, we confirmed that and were the most representative genera of BC tissue. are frequently and significantly enriched in the intestines of patients with breast tumor. The areas under the curve (AUCs) of random forest models were 74.27% and 68.08% for breast carcinoma tissues and stool samples, respectively. The model was validated for effectiveness cohort-to-cohort transfer (average AUC =0.65) and leave-one-cohort-out (average AUC = 0.66). The same BC-associated biomarker exists in the tissues and the gut. The results of the experiments showed that the -specific-related metabolite deoxycholic acid (DCA) promotes the proliferation of HER2-positive BC cells and stimulates G0/G1 phase cells to enter the S phase, which may be related to the activation of peptide-O-fucosyltransferase activity functions and the neuroactive ligand-receptor interaction pathway. The results of this study will improve our understanding of the microbial profile of breast tumors. Changes in the microbial population may be present in both the tissues and the gut of patients with BC, and specific markers could aid in the early diagnosis of BC. The findings from experiments confirmed that -specific metabolite DCA promotes the proliferation of BC cells. We propose the use of stool-based biomarkers in clinical application as a non-invasive and convenient diagnostic method.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: 16S rRNA / Bayes Theorem / Bile / Bioinformatics / Biomarkers / Biomarkers, Tumor / Breast cancer / Breast carcinoma / Breast diseases / Breast Neoplasms / cancer diagnosis / Cell growth / Cell proliferation / Cellular and Infection Microbiology / Clostridium / Clostridium - genetics / Confounding (Statistics) / Datasets / Deoxycholic acid / Deoxycholic Acid - pharmacology / Diagnosis / Digestive system / Dysbacteriosis / ErbB-2 protein / Feces / Female / G1 phase / Gastrointestinal Microbiome - physiology / Gastrointestinal tract / Genera / Gut microbiota / Humans / Intestinal microflora / intestine / microbiome / Microbiota / random forest / RNA, Ribosomal, 16S - genetics / rRNA 16S / S phase / Software / Tissues / Tumorigenesis / Tumors / Womens health