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| 外周血miR-338-5p、miR-140-5p在HBV相关肝细胞癌患者中表达水平及临床意义 |
| Expression levels and clinical significance of miR-338-5p and miR-140-5p in peripheral blood of patients with HBV-related hepatocellular carcinoma |
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| DOI：10.3969/j.issn.1007-8134.2023.04.04 |
| 中文关键词: 肝细胞癌 乙型肝炎病毒 微小RNA 微小RNA-338-5p 微小RNA-140-5p |
| 英文关键词: hepatocellular carcinoma hepatitis B virus microRNA microRNA-338-5p microRNA-140-5p |
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| 摘要点击次数: 94 |
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| 中文摘要: |
| 目的?探讨外周血血清中微小RNA（microRNA, miR）-338-5p、miR-140-5p在HBV相关肝细胞癌患者中表达水平及临床意义。方法?选取2017年11月—2020年11月我院收治的HBV相关肝细胞癌患者95例作为肝细胞癌组，另选取同时期HBV相关良性肝病患者100例作为良性组，及健康体检者100例作为对照组。采用实时荧光定量PCR检测外周血血清中miR-338-5p、miR-140-5p表达水平及HBV DNA载量，采用Pearson相关分析分析HBV相关肝细胞癌患者外周血血清中miR-338-5p、miR-140-5p表达水平与HBV DNA载量的关系，采用多因素Logistic回归模型分析影响HBV相关肝细胞癌发生的危险因素；ROC曲线分析miR-338-5p、miR-140-5p、异常凝血酶原-Ⅱ（abnormal prothrombin-Ⅱ, PIVKA-Ⅱ）表达对HBV相关肝细胞癌的诊断价值。结果?外周血血清中miR-338-5p、PIVKA-Ⅱ表达水平从高至低依次为肝细胞癌组[（2.73±0.88）、（103.14，319.19）mAU/ml]、良性组[（1.48±0.40）、（32.70，87.15）mAU/ml]、对照组[（1.00±0.27）、（10.36，16.82）mAU/ml]，外周血血清中miR-140-5p表达水平从高至低依次为对照组（1.00±0.25）、良性组（0.72±0.20）、肝细胞癌组（0.38±0.12），两两比较差异均具有统计学意义（P均＜0.05）；肝细胞癌组患者HBV DNA载量（144.97±47.32）明显高于良性组（75.66±21.91）（P＜0.05）。不同TNM分期患者间比较，外周血血清中miR-338-5p、PIVKA-Ⅱ表达水平及HBV DNA载量从高至低依次为TNM Ⅳ期、Ⅲ期、Ⅱ期、Ⅰ期，外周血血清中miR-140-5p表达水平从高至低依次为TNM Ⅰ期、Ⅱ期、Ⅲ期、Ⅳ期，两两比较差异均有统计学意义（P均＜0.05）。HBV相关肝细胞癌患者外周血血清中miR-338-5p表达水平与HBV DNA载量呈正相关（P＜0.05），而miR-140-5p表达水平与HBV DNA载量呈负相关（P＜0.05）。HBV相关肝细胞癌发生与患者有无糖尿病史、有无长期饮酒史、HBV DNA载量及外周血血清中miR-338-5p、miR-140-5p、PIVKA-Ⅱ表达水平有关（P均＜0.05）。多因素Logistic回归分析显示外周血血清中PIVKA-Ⅱ＞40 mAU/ml、miR-338-5p高表达、miR-140-5p低表达是影响HBV相关肝细胞癌发生的独立危险因素（P＜0.05）。外周血血清中miR-338-5p、miR-140-5p、PIVKA-Ⅱ表达水平联合诊断HBV相关肝细胞癌的AUC为0.930，明显高于3指标单独诊断的AUC（P均＜0.05），联合诊断的敏感度为98.90%，特异度为87.00%。结论?HBV相关肝细胞癌患者外周血血清中miR-338-5p高表达，miR-140-5p低表达，2者可作为评估HBV相关肝细胞癌发生的血清指标，2者联合PIVKA-Ⅱ更有利于诊断HBV相关肝细胞癌。 |
| 英文摘要: |
| Objective To investigate the expression levels and clinical significance of microRNA-338-5p (miR-338-5p) and microRNA-140-5p (miR-140-5p) in peripheral blood of patients with HBV hepatocellular carcinoma. Methods?Ninety-five patients with HBV hepatocellular carcinoma admitted to our hospital from November 2017 to November 2020 were selected as the hepatocellular carcinoma group, another one-hundred patients with HBV related benign liver disease in the same period were selected as the benign group, and 100 healthy people were selected as the control group. The expression levels of miR-338-5p, miR-140-5p and the carrying capacity of HBV DNA in peripheral blood serum were detected by real-time fluorescence quantitative PCR. Pearson test was used to analyze the relationship between the expression levels of miR-338-5p and miR-140-5p in peripheral blood serum of HBV hepatocellular carcinoma patients and HBV DNA carrying capacity, multivariate Logistic regression model was used to analyze the risk factors of HBV hepatocellular carcinoma. ROC curve was used to analyze the diagnostic value of miR-338-5p, miR-140-5p and abnormal prothrombin-Ⅱ (PIVKA-Ⅱ) expression in HBV hepatocellular carcinoma. Results?The expression levels of miR-338-5p and PIVKA-Ⅱ in peripheral blood serum from high to low was in hepatocellular carcinoma group [(2.73±0.88), (103.14, 319.19) mAU/ml], benign group [(1.48±0.40), (32.70, 87.15) mAU/ml] and control group [(1.00±0.27), (10.36, 6.82) mAU/ml], and the expression level of miR-140-5p in peripheral blood serum from high to low was in control group (1.00±0.25), benign group (0.72±0.20) and hepatocellular carcinoma group (0.38±0.12), the differences were statistically significant (P＜0.05); the carrying capacity of HBV DNA in hepatocellular carcinoma group (144.97±47.32) was significantly higher than that in benign group (75.66±21.91) (P＜0.05). The expression levels of miR-338-5p, PIVKA-Ⅱ and the carrying capacity of HBV DNA in peripheral blood from high to low were in the order of TNM stage IV, III, II and I, the expression level of miR-140-5p in peripheral blood serum from high to low was in TNM stage I, II, III and IV, and the differences were statistically significant (P＜0.05). The expression level of miR-338-5p in peripheral blood serum of HBV hepatocellular carcinoma patients was positively correlated with the carrying capacity of HBV DNA (P＜0.05), and the expression level of miR-140-5p was negatively correlated with the carrying capacity of HBV DNA (P＜0.05). The occurrence of HBV hepatocellular carcinoma was related to the history of diabetes, long-term drinking history, HBV DNA carrying capacity and the expression levels of miR-338-5p, miR-140-5p and PIVKA-Ⅱ in peripheral blood serum (P＜0.05). Multivariate Logistic regression analysis showed that PIVKA-Ⅱ＞40 mAU/ml, high expression of miR-338-5p and low expression of miR-140-5p in peripheral blood serum were independent risk factors for HBV hepatocellular carcinoma (P＜0.05). The area under the curve of the combined diagnosis of miR-338-5p, miR-140-5p and PIVKA-Ⅱ expression levels in peripheral blood serum for HBV hepatocellular carcinoma was 0.930, which was significantly higher than that of the single diagnosis of the 3 indicators (P＜0.05), the sensitivity of the combined diagnosis was 98.90%, and the specificity was 87.00%. Conclusions?MiR-338-5p is highly expressed, and miR-140-5p is downregulated in HBV-HCC patients. Both can serve as serum markers for evaluating HBV-HCC occurrence. The combination of them with PIVKA-Ⅱ is more conducive to the diagnosis of HBV hepatocellular carcinoma. |
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