Xiaodong Jia1, Shanshan Lu1, Zhen Zeng1, Qingyan Liu1, Zheng Dong1, Yan Chen1, Zhenyu Zhu2, Zhixian Hong3, Ting Zhang1, Guifang Du1, Jiao Xiang1, Dawei Wu1, Wenlin Bai1, Bin Yang1, Yinyin Li1, Jiagan Huang1, Haiyang Li4, Rifaat Safadi5, Yinying Lu1,6. 1. Comprehensive Liver Cancer Center, The Fifth Medical Center of PLA General Hospital, Beijing, China. 2. Hepatobiliary Surgery Center, The Fifth Medical Center of PLA General Hospital, Beijing, China. 3. Department of Hepatobiliary Surgery, The Fifth Medical Center of PLA General Hospital, Beijing, China. 4. Department of Hepatobiliary Surgery, The Hospital Affiliated to Guizhou Medical University, Guiyang, Guizhou, China. 5. Hadassah Medical Organization, Hadassah Hebrew University Medical Center, Jerusalem, Israel. 6. Center for Synthetic and Systems Biology (CSSB), Tsinghua University, Beijing, China.
Abstract
Intrahepatic cholangiocarcinoma (ICC), a type of bile duct cancer, has a high mortality rate. Gut microbiota, bile acid (BA) metabolism, and cytokines have not been characterized in patients with ICC, and better noninvasive diagnostic approaches for ICC are essential to be established. Therefore, in this study we aimed to improve our understanding of changes in gut microbiota, BA metabolism, and cytokines in patients with ICC. We found that the α-diversities and β-diversities of ICC were highest and that the abundances of four genera (Lactobacillus, Actinomyces, Peptostreptococcaceae, and Alloscardovia) were increased in patients with ICC compared with those in patients with hepatocellular carcinoma or liver cirrhosis and in healthy individuals. The glycoursodeoxycholic acid and tauroursodeoxycholic acid (TUDCA) plasma-stool ratios were obviously increased in patients with ICC. Furthermore, the genera Lactobacillus and Alloscardovia that were positively correlated with TUDCA plasma-stool ratios were combined to discriminate ICC from the other three diseases. Vascular invasion (VI) frequently led to a poor prognosis in patients with ICC. Compared with patients with ICC without VI, patients with VI had a greater abundance of the family Ruminococcaceae, increased levels of plasma interleukin (IL)-4 and six conjugated BAs, and decreased levels of plasma IL-6 and chenodeoxycholic acid. A positive correlation between plasma taurocholic acid and IL-4 was observed in patients with ICC. Plasma TUDCA was negatively correlated with the abundance of the genus Pseudoramibacter and the survival time of patients with ICC, but had no effect on tumor size, as determined in two murine tumor models. Conclusion: In this study, we identified some biomarkers, including gut microbiota, BAs and inflammatory cytokines, for the diagnosis of ICC and prediction of VI in patients with ICC.
Intrahepatic cholangiocarcinoma (ICC), a type of bile duct cancer, has a high mortality rate. Gut microbiota, bile acid (BA) metabolism, and cytokines have not been characterized in patients with ICC, and better noninvasive diagnostic approaches for ICC are essential to be established. Therefore, in this study we aimed to improve our understanding of changes in gut microbiota, BA metabolism, and cytokines in patients with ICC. We found that the α-diversities and β-diversities of ICC were highest and that the abundances of four genera (Lactobacillus, Actinomyces, Peptostreptococcaceae, and Alloscardovia) were increased in patients with ICC compared with those in patients with hepatocellular carcinoma or liver cirrhosis and in healthy individuals. The glycoursodeoxycholic acid and tauroursodeoxycholic acid (TUDCA) plasma-stool ratios were obviously increased in patients with ICC. Furthermore, the genera Lactobacillus and Alloscardovia that were positively correlated with TUDCA plasma-stool ratios were combined to discriminate ICC from the other three diseases. Vascular invasion (VI) frequently led to a poor prognosis in patients with ICC. Compared with patients with ICC without VI, patients with VI had a greater abundance of the family Ruminococcaceae, increased levels of plasma interleukin (IL)-4 and six conjugated BAs, and decreased levels of plasma IL-6 and chenodeoxycholic acid. A positive correlation between plasma taurocholic acid and IL-4 was observed in patients with ICC. Plasma TUDCA was negatively correlated with the abundance of the genus Pseudoramibacter and the survival time of patients with ICC, but had no effect on tumor size, as determined in two murinetumor models. Conclusion: In this study, we identified some biomarkers, including gut microbiota, BAs and inflammatory cytokines, for the diagnosis of ICC and prediction of VI in patients with ICC.
Authors: Elisa Herraez; Marta R Romero; Rocio I R Macias; Maria J Monte; Jose J G Marin Journal: Hepatobiliary Surg Nutr Date: 2020-04 Impact factor: 7.293
Authors: Roseanna C Wheatley; Elaine Kilgour; Timothy Jacobs; Angela Lamarca; Richard A Hubner; Juan W Valle; Mairéad G McNamara Journal: Br J Cancer Date: 2021-10-18 Impact factor: 9.075