血清miRNA-490-3p在慢性乙型肝炎病毒相关肝癌中的临床价值

Clinical value of serum miRNA-490-3p in chronic hepatitis B virus-related liver cancer

目的探讨血清miRNA-490-3p在慢性乙型肝炎病毒(HBV)相关肝癌中的临床价值。方法本研究为病例对照研究,选取2019年6月至2021年6月烟台市莱阳中心医院感染科收治的110例慢性HBV感染患者,男64例,女46例,年龄(55.90±5.73)岁,年龄范围为40~72岁,根据其疾病状态分为乙肝组(n=60)与肝癌组(n=50),乙肝组为慢性乙型肝炎患者,肝癌组为慢性乙型肝炎肝癌患者;另选取同期于烟台市莱阳中心医院体检中心行健康体检的55名纳入者作为健康组。检测三组纳入者血清miRNA-490-3p相对表达量,比较三组纳入者及不同临床病理特征肝癌患者的血清miRNA-490-3p表达差异。采用Pearson相关分析探讨血清miRNA-490-3p与乙型肝炎病毒的脱氧核糖核酸(HBV-DNA)载量、肝功能水平的相关性,同时采用受试者操作特征(ROC)曲线分析血清miRNA-490-3p诊断肝癌的临床价值。结果健康组、乙肝组及肝癌组纳入者血清总胆红素、白蛋白、丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、甲胎蛋白比较,差异有统计学意义(P<0.05);乙肝组HBV-DNA水平[(6.32±0.88)log10 IU/ml]低于肝癌组[(9.65±1.36)log10 IU/ml],差异有统计学意义(P<0.05)。健康组、乙肝组及肝癌组血清miRNA-490-3p相对表达量(7.82±0.88、5.63±0.73、4.31±0.65)比较,差异有统计学意义(P<0.05)。Pearson相关分析显示,肝癌组血清miRNA-490-3p相对表达量与白蛋白水平呈正相关,与ALT、AST、甲胎蛋白水平、HBV-DNA载量呈负相关。Child-Pugh分级B级患者血清miRNA-490-3p相对表达量(3.01±0.94)低于Child-Pugh分级A级患者(5.69±0.64),无转移患者血清miRNA-490-3p相对表达量(5.84±0.77)高于转移患者(2.88±1.10);无肝硬化患者血清miRNA-490-3p相对表达量(6.42±0.73)高于肝硬化患者(2.10±0.98),差异有统计学意义(P<0.05)。ROC曲线结果显示,血清miRNA-490-3p曲线下面积为0.722(95%CI:0.631~0.798,P<0.001),截断值为4.62,灵敏度为88.42%,特异度为75.63%;甲胎蛋白曲线下面积为0.642(95%CI:0.588~0.710,P<0.001),截断值为87.44、灵敏度为76.42%、特异度为64.74%。结论慢性HBV相关肝癌患者血清miRNA-490-3p水平降低,血清miRNA-490-3p对辅助诊断慢性HBV相关肝癌具有一定的临床价值,有望作为慢性HBV相关肝癌的临床生物标志物。

Objective To investigate the clinical value of serum miRNA-490-3p in chronic hepatitis B virus(HBV)related liver cancer.Methods This study was a case-control study.A total of 110 patients with chronic HBV infection,64 males and 46 females,aged(55.90±5.73)years old,ranging from 40 to 72 years old,were selected from the department of Infectious Disease in Yantai Laiyang Central Hospital from June 2019 to June 2021.According to their disease status,they were divided into hepatitis B group(n=60)and liver cancer group(n=50).The hepatitis B group was chronic hepatitis B patients,and the liver cancer group was chronic hepatitis B patients.In addition,a total of 55 participants who underwent physical examination in the physical examination center of Yantai Laiyang Central Hospital during the same period were selected as the health group.The relative expression of miRNA-490-3p in the serum of the three groups was detected,and the difference of miRNA-490-3p expression among the three groups and the patients with liver cancer with different clinical and pathological characteristics was compared.Pearson correlation analysis was used to investigate the correlation between serum miRNA-490-3p and hepatitis B virus-deoxyriboNucleic acid(HBV-DNA)load and liver function level,and receiver operating characteristic(ROC)curve was used to analyze the clinical value of serum miRNA-490-3p in the diagnosis of liver cancer.Results Comparison of serum total bilirubin,albumin,alanine aminotransferase(ALT),aspartate aminotransferase(AST)and alpha fetoprotein in health group,hepatitis B group and liver cancer group,the differencese were statistically significant(P<0.05);HBV-DNA in hepatitis B group[(6.32±0.88)log10 IU/ml]was lower than liver cancer group[(9.65±1.36)log10 IU/ml],the difference was statistically significant(P<0.05).Comparison of serum miRNA-490-3p relative expression in health group,hepatitis B group and liver cancer group(7.82±0.88,5.63±0.73,4.31±0.65),the differences were statistically significant(P<0.05).Pearson correlation analysis showed that the relative expression of miRNA-490-3p was positively correlated with albumin level,and negatively correlated with ALT,AST,alpha fetoprotein and HBV-DNA load.The relative expression of miRNA-490-3p in Child-Pugh grade B patients(3.01±0.94)was lower than that in Child-Pugh Grade A patients(5.69±0.64),and the relative expression of miRNA-490-3p in non-metastatic patients(5.84±0.77)was higher than that in metastatic patients(2.88±1.10),The relative expression of miRNA-490-3p in patients without cirrhosis(6.42±0.73)was higher than that in patients with cirrhosis(2.10±0.98),the differencese were statistically significant(P<0.05).The area under the curve of serum miRNA-490-3p was 0.722(95%CI:0.631 to 0.798,P<0.001),the cutoff value,sensitivity,and specificity were 4.62,88.42%and 75.63%,and the area under the curve of alpha fetoprotein was 0.642(95%CI:0.588 to 0.710,P<0.001),and the cutoff value,sensitivity,and specificity were respectively 87.44,76.42%and 64.74%.Conclusions The level of serum miRNA-490-3p in patients with chronic HBV-related liver cancer is significantly decreased,which gradually decrease as the disease progresses in patients with liver cancer.Serum miRNA-490-3p has certain clinical value in assisting the diagnosis of chronic HBV-related liver cancer,and is expected to serve as clinical biomarkers for chronic HBV related liver cancer.