PMID- 37089022 OWN - NLM STAT- MEDLINE DCOM- 20230425 LR - 20230427 IS - 1949-0984 (Electronic) IS - 1949-0976 (Print) IS - 1949-0976 (Linking) VI - 15 IP - 1 DP - 2023 Jan-Dec TI - A distinct microbiota signature precedes the clinical diagnosis of hepatocellular carcinoma. PG - 2201159 LID - 10.1080/19490976.2023.2201159 [doi] LID - 2201159 AB - Oral, gut, and tumor microbiota have been implicated as important regulators in the carcinogenesis and progression of gastrointestinal malignancies. However, few studies focused on the existence and association of resident microbes within different body regions. Herein, we aim to reveal the durability of the oral-gut-tumor microbiome and its diagnostic performance in hepatocellular carcinoma (HCC). Our study included two cohorts: a retrospective discovery cohort of 364 HBV-HCC patients and 160 controls with oral or fecal samples, a prospective validation cohort of 91 cases, and 124 controls for matching samples, as well as 48 HBV, and 39 HBV-cirrhosis patients for gut microbial patterns examined by 16S rRNA gene sequencing. With the random forest analysis, 10 oral and 9 gut genera that could distinguish HCC from controls in the retrospective cohort were validated among the prospective matching participants, with area under the curve (AUC) values of 0.7971 and 0.8084, respectively. When influential taxa were merged, the AUC of the consistent classifier increased to 0.9405. The performance continued to improve to 0.9811 when combined with serum levels of alpha-fetoprotein (AFP). Specifically, microbial biomarkers represented by Streptococcus displayed a constantly increasing trend during the disease transition. Furthermore, the presence of several dominant microbiota species was confirmed in hepatic tumor and non-tumor tissues with fluorescence in situ hybridization (FISH) and 5 R 16S rRNA gene sequencing. Overall, our findings based on the oral-gut-tumor microbiota provide a reliable approach for the early detection of HCC. FAU - Yang, Jinhuan AU - Yang J AD - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - He, Qikuan AU - He Q AD - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Lu, Fei AU - Lu F AD - The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, China. FAU - Chen, Kaiwen AU - Chen K AD - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Ni, ZhiHao AU - Ni Z AD - School of Nursing, Wenzhou Medical University, Wenzhou, China. FAU - Wang, Haoyue AU - Wang H AD - School of Mental Health, Wenzhou Medical University, Wenzhou, China. FAU - Zhou, Chen AU - Zhou C AD - The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, China. FAU - Zhang, Yaosheng AU - Zhang Y AD - The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, China. FAU - Chen, Bo AU - Chen B AD - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Bo, Zhiyuan AU - Bo Z AD - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Li, Jialiang AU - Li J AD - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Yu, Haitao AU - Yu H AD - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. FAU - Wang, Yi AU - Wang Y AD - Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University; Chashan High Education Zone, Wenzhou, China. FAU - Chen, Gang AU - Chen G AD - Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. AD - Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Gut Microbes JT - Gut microbes JID - 101495343 RN - 0 (RNA, Ribosomal, 16S) SB - IM MH - Humans MH - *Carcinoma, Hepatocellular/diagnosis/pathology MH - *Liver Neoplasms/diagnosis MH - Retrospective Studies MH - RNA, Ribosomal, 16S/genetics MH - In Situ Hybridization, Fluorescence MH - ROC Curve MH - *Gastrointestinal Microbiome/genetics MH - *Microbiota PMC - PMC10128432 OTO - NOTNLM OT - 16S rRNA gene OT - AFP OT - Microbiota OT - early detection OT - fluorescence in situ hybridization OT - hepatocellular carcinoma COIS- No potential conflict of interest was reported by the authors. EDAT- 2023/04/24 06:42 MHDA- 2023/04/25 10:20 PMCR- 2023/04/23 CRDT- 2023/04/24 02:12 PHST- 2023/04/25 10:20 [medline] PHST- 2023/04/24 06:42 [pubmed] PHST- 2023/04/24 02:12 [entrez] PHST- 2023/04/23 00:00 [pmc-release] AID - 2201159 [pii] AID - 10.1080/19490976.2023.2201159 [doi] PST - ppublish SO - Gut Microbes. 2023 Jan-Dec;15(1):2201159. doi: 10.1080/19490976.2023.2201159.