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肝硬化患者的磷脂谱与肝细胞癌风险及预后

Phospholipid profiles and hepatocellular carcinoma risk and prognosis in cirrhotic patients.

作者信息

Cotte Alexia Karen, Cottet Vanessa, Aires Virginie, Mouillot Thomas, Rizk Maud, Vinault Sandrine, Binquet Christine, de Barros Jean-Paul Pais, Hillon Patrick, Delmas Dominique

机构信息

University of Bourgogne, Franche-Comté, Dijon, France.

INSERM U1231 "Lipids, Nutrition, Cancer", Research Team Cancer and Adaptive Immune Response (CADIR), Dijon, France.

出版信息

Oncotarget. 2019 Mar 15;10(22):2161-2172. doi: 10.18632/oncotarget.26738.

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Phospholipids are now well-recognised players in tumour progression. Their metabolic tissue alterations can be associated with plasmatic modifications. The aim of this study was to evaluate the potential of the plasma phospholipid profile as a risk and prognostic biomarker in HCC.

METHODS

Ninety cirrhotic patients with (cases) or without HCC (controls) were studied after matching for inclusion centre, age, gender, virus infection, cirrhosis duration and Child-Pugh grade. High-performance liquid chromatography coupled with tandem-mass spectrometry was used to quantify the main species of seven categories of phospholipids in plasma.

RESULTS

Elevated concentrations of phosphatidylcholine (PC) 16:0/16:1 (p=0.0180), PC 16:0/16:0 (p=0.0327), PC 16:0/18:1 (p=0.0264) and sphingomyelin (SM) 18:2/24:1 (p=0.0379) and low concentrations of lysophosphatidylcholine 20:4 (0.0093) and plasmalogen-phosphatidylethanolamine (pPE) 16:0/20:4 (p=0.0463), pPE 18:0/20:4 (p=0.0077), pPE 18:0/20:5 (p=0.0163), pPE 18:0/20:3 (p=0.0463) discriminated HCC patients from cirrhotic controls. Two ceramide species were associated with increased HCC risk of death while lysophospholipids, a polyunsaturated phosphatidylinositol, some PC and SM species were associated with low risk of death in HCC patients in 1 and/or 3 years.

CONCLUSION

This study identified phospholipid profiles related to HCC risk in liver cirrhotic patients and showed for the first time the potential of some phospholipids in predicting HCC patient mortality.

摘要

背景

肝细胞癌(HCC)是全球第五大常见癌症。磷脂现在被公认为肿瘤进展中的关键因素。其代谢组织改变可能与血浆变化相关。本研究旨在评估血浆磷脂谱作为HCC风险和预后生物标志物的潜力。

方法

对90例肝硬化患者进行研究,根据纳入中心、年龄、性别、病毒感染、肝硬化病程和Child-Pugh分级进行匹配,分为有HCC组(病例组)和无HCC组(对照组)。采用高效液相色谱-串联质谱法对血浆中七类磷脂的主要种类进行定量分析。

结果

磷脂酰胆碱(PC)16:0/16:1(p = 0.0180)、PC 16:0/16:0(p = 0.0327)、PC 16:0/18:1(p = 0.0264)和鞘磷脂(SM)18:2/24:1(p = 0.0379)浓度升高,溶血磷脂酰胆碱20:4(0.0093)和缩醛磷脂酰乙醇胺(pPE)16:0/20:4(p = 0.0463)、pPE 18:0/20:4(p = 0.0077)、pPE 18:0/20:5(p = 0.0163)、pPE 18:0/20:3(p = 0.0463)浓度降低,可区分HCC患者与肝硬化对照组。两种神经酰胺种类与HCC患者死亡风险增加相关,而溶血磷脂、一种多不饱和磷脂酰肌醇、一些PC和SM种类与HCC患者1年和/或3年内的低死亡风险相关。

结论

本研究确定了与肝硬化患者HCC风险相关的磷脂谱,并首次显示了某些磷脂在预测HCC患者死亡率方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de91/6481329/19af31c9baf1/oncotarget-10-2161-g001.jpg

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