A prognostic fingerprint in liver transplantation for hepatocellular carcinoma based on plasma metabolomics profiling |
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| Affiliation: | 1. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China;2. Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Hangzhou, 310000, China;3. Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, 310000, China;1. Department of Neurosurgery, China National Clinical Research Center for Neurological Diseases (NCRC-ND), Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing Key Laboratory of Brian Tumor, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, PR China;2. Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, PR China;1. Belgian Cancer Registry, Rue Royale 215, Koningstraat 215 – 1210, Bruxelles, Brussel, Belgium;2. Belgian Health Care Knowledge Centre (KCE). Centre Administratif Botanique, Doorbuilding, Boulevard du Jardin Botanique 55, B-1000, Brussels, Belgium;3. Department of Respiratory Medicine, University Hospitals KU Leuven, Herestraat 49, 3000, Leuven, Belgium;4. Faculty of Medicine & Health Sciences, University of Antwerp, Antwerp University Hospital, Universiteitsplein 1, 2610, Antwerp, Belgium;5. Department of Pulmonology & Thoracic Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium;6. European Reference Network (ERN-LUNG/EURACAN);7. Department of Thoracic Surgery, University Hospitals KU Leuven, Herestraat 49, 3000, Leuven, Belgium;1. Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China;2. Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China;3. Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China;4. Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China;5. Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Caner Center, Guangzhou, China;1. Colorectal Surgery Unit, Peter MacCallum Cancer Centre, Melbourne, Australia;2. Colorectal Surgery Unit, Christchurch Hospital, Christchurch, New Zealand;1. Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital, POB 4950 Nydalen, N-0424, Oslo, Norway;2. K.G. Jebsen Colorectal Cancer Research Centre, Oslo University Hospital, POB 4950 Nydalen, N-0424, Oslo, Norway;3. Institute for Clinical Medicine, University of Oslo, POB 1171 Blindern, N-0318, Oslo, Norway;4. Department of Radiology and Nuclear Medicine, Oslo University Hospital, POB 4950 Nydalen, N-0424, Oslo, Norway;5. Department of Gastrointestinal Surgery, Oslo University Hospital, POB 4950 Nydalen, N-0424, Oslo, Norway;6. Department of Oncology, Oslo University Hospital, POB 4956 Nydalen, N-0424, Oslo, Norway |
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| Abstract: | IntroductionTumor 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 methodsMetabolomics profiling was performed on pre-operative plasma from 122 HCC patients undergoing liver transplantation, 52 healthy controls (HC) and 25 liver cirrhosis (LC) patients.ResultsFive 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).ConclusionsThe 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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| Keywords: | Metabolomics Hepatocellular carcinoma Liver transplantation Fingerprint Nomogram |
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