肝细胞癌中脂代谢的重新编程导致磷脂酰胆碱下调,可用作诊断和预测的潜在标志物。
Reprogramming of lipid metabolism in hepatocellular carcinoma resulting in downregulation of phosphatidylcholines used as potential markers for diagnosis and prediction.
发表日期:2023 Sep 06
作者:
Kang Li, Wanting Shi, Yi Song, Lin Qin, Chaoran Zang, Tingting Mei, Ang Li, Qingkun Song, Yonghong Zhang
来源:
EXPERT REVIEW OF MOLECULAR DIAGNOSTICS
摘要:
异常的甲基化和代谢紊乱可以加深我们对肝癌发生机制的理解,并有助于诊断肝细胞癌(HCC)的新型生物标志物的鉴定。我们旨在基于多组学开发 HCC 模型。对 400 个患者样本(其中 200 例患有 HCC,200 例患有乙型肝炎病毒相关的肝病(HBVLD)),进行了液相色谱质谱分析和多重亚硫酸盐测序。通过对 20 个完整插值数据集进行临床数据、CpG 数据和代谢谱数据的综合分析,在 for 循环内用于鉴定生物标志物。总共注释了 1,140 个代谢物,其中有 125 个差异表达。HCC 中的脂质代谢重编程导致磷脂酰胆碱(PC)显著下调,部分原因是由于线长不同的脂肪酸改变的线粒体β-氧化。年龄、性别、血清甲胎蛋白水平、cg05166871、cg14171514、cg18772205、PC(O-16:0/20:3(8Z, 11Z, 14Z))和 PC(16:1(9Z)/P-18:0)被用于开发 HCC 模型。该模型具有良好的诊断性和可接受的预测性能。HBVLD 患者低风险组和高风险组的 HCC 累积发生率分别为 1.19% 和 21.40%(p = 0.0039)。PCs 可作为潜在的血浆生物标志物,并有助于识别 HBVLD 患者中患有 HCC 风险的个体,应进行早期筛查和干预。
Aberrant methylation and metabolic perturbations may deepen our understanding of hepatocarcinogenesis and help identify novel biomarkers for diagnosing hepatocellular carcinoma (HCC). We aimed to develop an HCC model based on a multi-omics.Four hundred patient samples (200 with HCC and 200 with hepatitis B virus-related liver disease (HBVLD)) were subjected to liquid chromatography-mass spectrometry and multiplex bisulfite sequencing. Integrative analysis of clinical data, CpG data, and metabolome for the 20 complete imputation datasets within a for-loopwas used to identify biomarker.Totally, 1,140 metabolites were annotated, of which 125 were differentially expressed. Lipid metabolism reprogramming in HCC, resulting in phosphatidylcholines (PC) significantly downregulated, partly due to the altered mitochondrial beta-oxidation of fatty acids with diverse chain lengths. Age, sex, serum-fetoprotein levels, cg05166871,cg14171514, cg18772205, PC (O-16:0/20:3(8Z, 11Z, 14Z)), and PC (16:1(9Z)/P-18:0) were used to develop the HCC model. The model presented a good diagnostic and an acceptable predictive performance. The cumulative incidence of HCC in low- and high-risk groups of HBVLD patients were 1.19% and 21.40%, respectively (p = 0.0039).PCs serve as potential plasma biomarkers and help identify patients with HBVLD at risk of HCC who should be screened for early diagnosis and intervention.