PT  - JOURNAL ARTICLE
AU  - Jinkai Liu
AU  - Wei Geng
AU  - Hanyong Sun
AU  - Changan Liu
AU  - Fan Huang
AU  - Jie Cao
AU  - Lei Xia
AU  - Hongchuan Zhao
AU  - Jianning Zhai
AU  - Qing Li
AU  - Xiang Zhang
AU  - Ming Kuang
AU  - Shunli Shen
AU  - Qiang Xia
AU  - Vincent Wai-Sun Wong
AU  - Jun Yu
TI  - Integrative metabolomic characterisation identifies altered portal vein serum metabolome contributing to human hepatocellular carcinoma
AID  - 10.1136/gutjnl-2021-325189
DP  - 2022 Jun 01
TA  - Gut
PG  - 1203--1213
VI  - 71
IP  - 6
4099  - http://gut.bmj.com/content/71/6/1203.short
4100  - http://gut.bmj.com/content/71/6/1203.full
SO  - Gut2022 Jun 01; 71
AB  - Objective Altered metabolites are important for the tumourigenicity of hepatocellular carcinoma (HCC). We performed integrative metabolomics analysis of the metabolites changes in portal venous blood and in comparison with the metabolites changes in liver tissues and stool samples of HCC patients and healthy liver donors.Design Serum (portal and central vein), liver tissue (HCC tumour and adjacent non-tumour, normal liver) and stool samples were collected from 102 subjects (52 HCC patients and 50 healthy controls) in the discovery cohort; and 100 subjects (50 HCC patients and 50 healthy controls) in an independent validation cohort. Untargeted metabolomic profiling was performed using high-performance liquid chromatography-mass spectrometry. The function of candidate metabolites was validated in hepatocyte cell lines.Results Detailed metabolomic evaluation showed distinct clusters of metabolites in serum, liver tissue and stool samples from patients with HCC and control individuals (p<0.001). HCC patients had significantly higher levels of portal vein serum and HCC tissue metabolites of DL-3-phenyllactic acid, L-tryptophan, glycocholic acid and 1-methylnicotinamide than healthy controls, which were associated with impaired liver function and poor survival. On the other hand, HCC patients had lower levels of linoleic acid and phenol in portal vein and stool samples than healthy controls. Linoleic acid and phenol significantly inhibited HCC proliferation, inferring their anti-HCC function as protective metabolites.Conclusions The integrative metabolome analysis of serum, tissue and stool metabolites revealed unreported metabolic alterations in HCC patients. In portal vein, we identified elevated and depleted metabolites signifying that they might play a role in HCC development.Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as online supplemental information. Data are available on reasonable request.