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A prognostic fingerprint in liver transplantation for hepatocellular carcinoma based on plasma metabolomics profiling
Di Lu1, Fan Yang1, Zuyuan Lin1
1Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China; Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China.
Introduction:
Tumor recurrence is a major cause of post-transplant mortality in liver transplantation for hepatocellular carcinoma (HCC). This study aimed to explore an effective noninvasive approach to accurately predict post-transplant tumor recurrence.
Materials And Methods:
Metabolomics profiling was performed on pre-operative plasma from 122 HCC patients undergoing liver transplantation, 52 healthy controls (HC) and 25 liver cirrhosis (LC) patients.
Results:
Five prognostic metabolites were identified by univariate analysis (P < 0.01), including phosphatidylcholine (PC) (16:0/P-18:1), PC(18:2/OH-16:0), PC(o-16:0/20:4), nutriacholic acid and 2-oxo-4-methylthiobutanoic acid. In the HCC group, PC(o-16:0/20:4), nutriacholic acid and 2-oxo-4-methylthiobutanoic acid were decreased, while PC(18:2/OH-16:0) was elevated compared with the LC group (e < 0.05). PC(16:0/P-18:1) was associated with tumor size, vascular invasion, and neutrophil-lymphocyte ratio (NLR; P < 0.05). Moreover, PC(18:2/OH-16:0) was also related to tumor number and NLR (P < 0.05). Multivariate cox regression showed that PC(16:0/P-18:1), PC(18:2/OH-16:0), nutriacholic acid and alpha-fetoprotein (AFP) were independent risk factors for tumor recurrence (P < 0.01). A prognostic fingerprint was established as a nomogram, which divided the patients into low risk (n = 45), moderate risk (n = 48) and highrisk groups (n = 29) with discriminated prognosis (P < 0.001). In patients fulfilling the Hangzhou criteria, the fingerprint/nomogram could also successfully stratify the patients into two groups with different recurrence risk (P < 0.05).
Conclusions:
The established pre-operative plasma fingerprint/nomogram is efficient in the prediction of recurrence risk, which could facilitate candidate selection in liver transplantation for HCC.
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