腹水和血清细胞外囊泡内容物联合检测HBV相关原发性肝细胞癌的诊断价值

Diagnostic value of combined detection of ascites and serum extracellular vesicle contents for HBV-related primary hepatocellular carcinoma

    摘要
  • 摘要:
    目的  探究腹水和血清细胞外囊泡(EVs)中微小核糖核酸(miRNA)与甲胎蛋白(AFP)、维生素K缺乏或拮抗剂诱导蛋白Ⅱ(PIVKA-Ⅱ)联合检测乙型肝炎病毒(HBV)相关原发性肝细胞癌(HCC)的诊断价值。
    方法  选取2023年11月-2024年11月解放军总医院第五医学中心收治的腹水放置或腹水浓缩回流术的肝癌患者41例和肝硬化患者26例为研究对象，留取患者腹水及血清标本。采用实时定量逆转录聚合酶链反应(qRT-PCR)技术检测细胞外囊泡的miR-21、miR-125a、miR-150、miR-200a表达水平，化学发光法检测腹水和血清及腹水EVs和血清EVs中AFP和PIVKA-Ⅱ的含量。利用人工神经网络，构建血清标记物联合腹水标记物诊断模型。
    结果  血清联合各指标鉴别HCC与肝硬化的曲线下面积(AUC)为0.933，腹水联合各指标鉴别HCC与肝硬化的AUC为0.912，利用人工神经网络筛选所有检测指标，将相对重要性＞0.5的指标纳入诊断模型中，模型包含腹水AFP，腹水EVs miR-21，腹水EVs miR-200a，血清EVs miR-200a共4个指标，区分HCC与肝硬化患者的灵敏度为80.77%，特异度为87.80%，AUC为0.960。
    结论  腹水和血清来源EVs miRNA与AFP、PIVKA-Ⅱ联合诊断标记物在诊断HCC中具有良好的应用价值。

     

    Abstract:
    OBJECTIVE  To explore the diagnostic value of combined detection of microRNA (miRNA) and alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) in ascites and serum extracellular vesicles (EVs) for hepatitis B virus (HBV)-related primary hepatocellular carcinoma (HCC).
    METHODS  From Nov. 2023 to Nov. 2024, 41 patients with liver cancer and 26 patients with liver cirrhosis who underwent ascites placement or ascites concentration and reinfusion procedures at the Fifth Medical Center of Chinese PLA General Hospital were selected as study subjects. Ascites and serum samples were collected. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-21, miR-125a, miR-150 and miR-200a in EVs. Chemiluminescence was used to measure the levels of AFP and PIVKA-Ⅱ in ascites, serum and EVs from ascites and serum. An artificial neural network was utilized to construct a combined diagnostic model of serum and ascites markers.
    RESULTS  The area under the curve (AUC) for distinguishing HCC from liver cirrhosis using a combination of serum and other indicators was 0.933. The AUC for distinguishing HCC from liver cirrhosis using a combination of ascites and other indicators was 0.912. By screening all detected indicators using an artificial neural network and incorporating indicators with a relative importance >0.5 into the diagnostic model, the model included four indicators: ascites AFP, ascites EVs miR-21, ascites EVs miR-200a and serum EVs miR-200a. This model had a sensitivity of 80.77%, a specificity of 87.80% and an AUC of 0.960 for distinguishing HCC from liver cirrhosis patients.
    CONCLUSION  The combined diagnostic markers of miRNA, AFP and PIVKA-Ⅱ in ascites and serum-derived EVs have good application value in the diagnosis of HCC.

     

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