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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients
Min-Woo Chung, Moon-Ju Kim, Eun Jeong Won, Yu Jeong Lee, Yong-Woon Yun, Sung Bum Cho, Young-Eun Joo, Jun-Eul Hwang, Woo Kyun Bae, Ik-Joo Chung, Myung Geun Shin, Jong Hee Shin
Min-Woo Chung, Sung Bum Cho, Young-Eun Joo, Jun-Eul Hwang, Woo Kyun Bae, Ik-Joo Chung, Department of Internal Medicine, Chonnam National University Hospital and College of Medicine, Hwasun 58128, Jeollanam-do, South Korea
Moon-Ju Kim, Eun Jeong Won, Yu Jeong Lee, Department of Parasitology and Tropical Medicine, Chonnam National University Medical School, Hwasun 58128, Jeollanam-do, South Korea
Eun Jeong Won, Myung Geun Shin, Department of Laboratory Medicine, Chonnam National University Hwasun Hospital, Hwasun 58128, Jeollanam-do, South Korea
Yong-Woon Yun, Department of Preventive Medicine, Chonnam National University Medical School, Hwasun-eup, Hwasun 58128, Jeollanam-do, South Korea
Jong Hee Shin, Department of Laboratory Medicine, Chonnam National University Hospital, Gwangju 61469, South Korea
Author contributions: Won EJ conceived of the study, participated in the study design and data analysis, and was responsible for writing and submission of the final manuscript; Kim MJ and Lee YJ carried out the experimental studies; Chung MW, Cho SB, Joo Y, Yun YW and Kim MJ analyzed and interpreted the data; Yun YW interpreted the statistical data; Hwang JE, Bae WK, Chung IJ, Shin MG and Shin JH were responsible for patient care and sample acquisition; All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published.
Supported by the National Research Foundation of Korea (NRF) Grant funded by the Ministry of Education, Science, and Technology, No. NRF-2019R1C1C1004605, No. NRF-2019M3E5D1A02067953, and No. NRF-2021M3E5D1A0201518021.
Institutional review board statement: This study was carried out in accordance with all relevant institutional guidelines. The Ethics Committee of Chonnam National University Hwasun Hospital approved this study (CNUHH-2019-134) and written informed consent was obtained from all subjects.
Conflict-of-interest statement: All authors declare having no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Eun Jeong Won, MD, PhD, Professor, Department of Parasitology and Tropical Medicine, Chonnam National University Medical School, 322, Seoyang-ro, Hwasun-eup, Hwasun 58128, Jeollanam-do, South Korea.
parasite.woni@jnu.ac.kr
Received: May 20, 2021
Peer-review started: May 20, 2021
First decision: June 13, 2021
Revised: June 18, 2021
Accepted: November 3, 2021
Article in press: November 3, 2021
Published online: November 14, 2021
Processing time: 173 Days and 20.5 Hours
ARTICLE HIGHLIGHTS
Research background
Systemic chemotherapy for hepatocellular carcinoma (HCC) has an important role, and immunotherapy in HCC is challenging.
Research motivation
Predictive or prognostic markers for systemic treatment for HCC have not been elucidated.
Research objectives
To investigate the correlation between gut microbiome and treatment response in advanced HCC.
Research methods
Patients who were treated with nivolumab for HCC were identified from one tertiary hospital in South Korea from September 2019 to August 2020. Metagenomic data from 16S ribosomal RNA sequencing were analyzed according to therapeutic response.
Research results
A higher Shannon index was found in the responders than in the non-responders after nivolumab therapy (P = 0.036). The unweighted beta diversity analysis also showed that the overall bacterial community structure and phylogenetic diversity were clearly distinguished according to therapeutic response. A skewed Firmicutes/Bacteroidetes ratio and a low Prevotella/Bacteroides ratio can serve as predictive markers of non-response, whereas the presence of Akkermansia species predicts a good response.
Research conclusions
Gut microbiome has a potential role as a prognostic marker for the response to nivolumab in the treatment of HCC patients.
Research perspectives
Microbiome study before and/or follow up of treatment with immunotherapy for HCC patients could be a prognostic marker, and it can be a criterion for selecting which systemic treatment should be used for each patient as part of precision medicine.
