血清VEGF、miR-122、GDF15及TK1在乙肝相关性肝病表达水平及其临床意义

摘要 目的：分析不同类型乙肝相关性肝病患者血清血管内皮生长因子（VEGF）、microRNA-122（miR-122）、生长分化因子15（GDF-15）及胸苷激酶1（TK1）的表达差异变化及其临床意义。方法：随机选取2020年1月-2022年6月在我院消化内科收治的不同类型乙肝相关性肝病患者135例作为研究组。其中根据乙型肝炎诊断标准分为慢性乙型肝炎组（CHB）76例，乙型肝炎肝硬化组（LC）57例，乙型肝炎肝癌组（HCC）78例，选取同时期在本院进行体检的健康受检者96例作为健康组。比较各组的基本资料、检测研究对象血清VEGF、miR-122、GDF15、TK1、HBV DNA载量水平和AFP表达水平。采用Pearson相关性检验分析乙肝相关性肝病患者血清VEGF、miR-122、GDF15及TK1表达水平与HBV DNA载量水平的相关性，采用受试者工作特征曲线（ROC）诊断LC和HCC的价值。结果：CHB 组、LC 组 和HCC组VEGF、TK1表达水平显著高于健康组，差异具有统计学意义（P<0.01），CHB 组、LC 组 和HCC组组间两两比较，差异具有统计学意义（P<0.01）。CHB 组、LC 组 和HCC组miR-122表达水平显著低于健康组，差异具有统计学意义（P<0.01），CHB 组、LC 组 和HCC组组间两两比较，差异具有统计学意义（P<0.01）。LC 组 和HCC组GDF15表达水平显著高于 CHB 组和健康组，差异具有统计学意义（P<0.01），CHB 组和健康组组间比较差异无统计学意义（P>0.05）。CHB 组、LC 组 和HCC组HBV DNA载量水平显著高于健康组，差异具有统计学意义（P<0.01），LC 组 和HCC组组间比较，差异无统计学意义（P>0.05）。LC 组 和HCC组AFP表达水平显著高于 CHB 组和健康组，差异具有统计学意义（P<0.01），LC 组 和HCC组、CHB 组和健康组组间比较差异无统计学意义（P>0.05）。CHB组、LC+HCC组血清VEGF、miR-122、GDF15及TK1水平与HBV DNA载量水平具有相关性（P<0.01或P<0.05）。血清VEGF、miR-122、GDF15及TK1单独检测诊断LC和HCC的曲线下面积（AUC）为0.695、0.783、0.743及0.7687，四项指标联合检测诊断LC和HCC的AUC为0.839，敏感度为84.21，特异度为83.25。结论：血清VEGF、miR-122、GDF15及TK1在各类型乙肝相关性肝病中表达水平存在差异，血清VEGF、miR-122、GDF15及TK1联合检测诊断LC和HCC具有临床价值。

Expression of Serum VEGF, miR-122, GDF15 and TK1 in Hepatitis B Related Liver Diseases and their Clinical Significance

ABSTRACT Objective: To analyze the differential expression of serum vascular endothelial growth factor (VEGF), microRNA-122 (miR-122), growth differentiation factor 15 (GDF-15) and thymidine kinase 1 (TK1) in patients with different types of hepatitis B related liver diseases and their clinical significance. Methods: 135 patients with different types of hepatitis B related liver diseases admitted to the Department of Gastroenterology in our hospital from January 2020 to June 2022 were randomly selected as the study group. According to the diagnostic criteria of hepatitis B, 76 patients were divided into chronic hepatitis B group (CHB), 57 patients were divided into hepatitis B cirrhosis group (LC) and 78 patients were divided into hepatitis B liver cancer group (HCC). 96 healthy subjects who underwent physical examination in our hospital at the same time were selected as the healthy group. The basic data of each group were compared, and the levels of serum VEGF, miR-122, GDF15, TK1, HBV DNA load and AFP expression were detected. Pearson correlation test was used to analyze the correlation between the expression levels of serum VEGF, miR-122, GDF15 and TK1 and HBV DNA load in patients with hepatitis B related liver disease. The value of receiver operating characteristic curve (ROC) in diagnosing LC and HCC was used. Results: the expression levels of VEGF and TK1 in CHB group, LC group and HCC group were significantly higher than those in healthy group(P<0.01). There was significant difference between CHB group, LC group and HCC group(P<0.01). The expression level of miR-122 in CHB group, LC group and HCC group was significantly lower than that in healthy group (P<0.01), and there was significant difference between CHB group, LC group and HCC group (P<0.01). The expression level of GDF15 in LC group and HCC group was significantly higher than that in CHB group and healthy group (P<0.01), but there was no significant difference between CHB group and healthy group (P>0.05). HBV DNA load level in CHB group, LC group and HCC group was significantly higher than that in healthy group (P<0.01), but there was no significant difference between LC group and HCC group (P>0.05). The expression level of AFP in LC group and HCC group was significantly higher than that in CHB group and healthy group (P<0.01). There was no significant difference between LC group and HCC group, CHB group and healthy group (P>0.05). The levels of serum VEGF, miR-122, GDF15 and TK1 in CHB group and lc+hcc group were correlated with HBV DNA load (P<0.01 or P<0.05). The area under the curve (AUC) of serum VEGF, miR-122, GDF15 and TK1 in the diagnosis of LC and HCC was 0.695, 0.783, 0.743 and 0.7687 respectively. The AUC of the combined detection of these four indicators in the diagnosis of LC and HCC was 0.839, with a sensitivity of 84.21 and a specificity of 83.25. Conclusion: There are differences in the expression levels of serum VEGF, miR-122, GDF15 and TK1 in various types of hepatitis B related liver diseases. The combined detection of serum VEGF, miR-122, GDF15 and TK1 has clinical value in the diagnosis of LC and HCC.