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血清鞘脂用于乙肝相关甲胎蛋白阴性肝细胞癌的诊断价值研究

The diagnostic value of serum sphingolipids for HBV-related AFP negative hepatocellular carcinoma

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【作者】 蒋莹莹铁偲王扬程香普卞丹丹王婷刘梅段钟平郑素军张金兰

【Author】 JIANG Yingying;TIE Cai;WANG Yang;CHENG Xiangpu;BIAN DANDan;WANG Ting;LIU Mei;DUAN Zhongping;ZHENG Sujun;ZHANG Jinlan;Severe Liver Disease and Artificial Liver Center,Beijing Youan Hospital,Capital Medical University;The Institute of Materia Medical,Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC);The Institute of Materia Medical,Chinese Academy of Medical Sciences(CAMS) & Peking Union Medical College (PUMC);

【机构】 首都医科大学附属北京佑安医院疑难肝病与人工肝中心协和医科大学中国医学科学院药物研究所

【摘要】 目的探讨乙型肝炎病毒(hepatitis B virus,HBV)相关甲胎蛋白(AFP)阴性肝细胞癌(hepatocellular carcinoma,HCC)患者血清鞘脂表达谱改变及其诊断价值。方法采用高效液相色谱法与串联质谱法,对15例乙肝相关AFP阴性HCC患者和49例乙肝肝硬化患者的外周血清中61种鞘脂的表达水平进行检测,并对结果进行统计分析。结果 61种血清鞘脂中,有14种鞘脂在两组间差异有统计学意义(P<0.05)。OPLSDA分析结果表明,Cer(d18∶1/8∶0)-1-P、Sphingosine(d17∶1)-1-P和Sphingosine(d18∶1)-1-P是区分乙肝相关AFP阴性HCC和乙肝肝硬化的潜在标志物,其在AFP阴性HCC患者中的表达水平分别为217.74pmol/0.1 ml、58.28 pmol/0.1 ml和62.99 pmol/0.1 ml,均显著高于乙肝肝硬化患者的表达水平(P<0.05)。将三种鞘脂纳入Logistics回归分析,结果表明,Cer(d18∶1/8∶0)-1-P与乙肝相关AFP阴性HCC独立相关(OR=0.667,95%CI:0.481~0.923,P<0.05),其预测诊断乙肝相关AFP阴性HCC的灵敏度为81.6%,特异度为86.7%。结论外周血清鞘脂Cer(d18∶1/8∶0)-1-P可能是乙肝相关AFP阴性HCC的潜在诊断标志物。

【Abstract】 Objective To explore the diagnostic value of serum sphingolipids for HBV-related AFP negative hepatocellular carcinoma(HCC). Methods Fifteen patients with HBV-related AFP negative HCC and 49 HBV-related liver cirrhotic patients were enrolled in this study. The expression levels of 61 serum sphingolipids were detected by highperformance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Results Among 61 kinds of sphingolipids,14 kinds of sphingolipids had significant differences between two groups(P < 0. 05). The results of OPLSDA analysis showed that Cer(d18∶ 1/8∶ 0)-1-P,Sphingosine(d17∶ 1)-1-P and Sphingosine(d18∶ 1)-1-P had the potential to differentiate HBV-related AFP negative HCC from cirrhosis,and their expression levels in HBV-related AFP negative HCC patients were 217. 74 pmol/0. 1 ml,58. 28 pmol/0. 1 ml and 62. 99 pmol/0. 1 ml,respectively,which were significantly higher than those in HBV-related cirrhosis(P < 0. 05). These 3 sphingolipids were further included in the Logistic regression analysis and the results showed that Cer(d18 ∶ 1/8 ∶ 0)-1-P was independently associated with HBVrelated AFP negative HCC(OR = 0. 667,95% CI: 0. 481-0. 923,P < 0. 05),and its sensitivity and specificity for predicting HBV-related AFP negative HCC were 81. 6%,86. 7%,respectively. Conclusion Up-regulation of Cer(d18∶ 1/8∶ 0)-1-P levels in serum may be used to identify HBV-related AFP-negative HCC.

【基金】 北京市科学技术委员会资助临床特色项目(Z151100004015066);十三五国家科技攻关项目(2017ZX10302201-004,2017ZX10202203-006,2017ZX10201201);北京市医管局临床技术创新项目(XMLX201830)
  • 【文献出处】 胃肠病学和肝病学杂志 ,Chinese Journal of Gastroenterology and Hepatology , 编辑部邮箱 ,2018年05期
  • 【分类号】R512.62;R735.7
  • 【被引频次】2
  • 【下载频次】90
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