Division 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.
Division 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; Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, 310000, China.
Eur J Surg Oncol. 2019 Dec;45(12):2347-2352. doi: 10.1016/j.ejso.2019.07.004. Epub 2019 Jul 2.
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.
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.
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).
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.
肿瘤复发是肝癌患者肝移植后移植后死亡的主要原因。本研究旨在探索一种准确预测移植后肿瘤复发的有效无创方法。
对 122 例接受肝移植的 HCC 患者、52 例健康对照（HC）和 25 例肝硬化（LC）患者的术前血浆进行代谢组学分析。
通过单因素分析确定了 5 个预后代谢物（P < 0.01），包括磷脂酰胆碱（PC）（16:0/P-18:1）、PC（18:2/OH-16:0）、PC（o-16:0/20:4）、牛磺胆酸和 2-氧代-4-甲基硫代丁酸。在 HCC 组中，与 LC 组相比，PC（o-16:0/20:4）、牛磺胆酸和 2-氧代-4-甲基硫代丁酸降低，而 PC（18:2/OH-16:0）升高（e < 0.05）。PC（16:0/P-18:1）与肿瘤大小、血管侵犯和中性粒细胞-淋巴细胞比值（NLR；P < 0.05）相关。此外，PC（18:2/OH-16:0）也与肿瘤数量和 NLR 相关（P < 0.05）。多因素 Cox 回归显示，PC（16:0/P-18:1）、PC（18:2/OH-16:0）、牛磺胆酸和甲胎蛋白（AFP）是肿瘤复发的独立危险因素（P < 0.01）。建立了一个预测指纹的列线图，将患者分为低危（n = 45）、中危（n = 48）和高危组（n = 29），并具有不同的预后（P < 0.001）。在符合杭州标准的患者中，指纹/列线图也能成功地将患者分为两组，具有不同的复发风险（P < 0.05）。
建立的术前血浆指纹/列线图在预测复发风险方面具有较高的效率，可有助于 HCC 患者肝移植的候选者选择。
