miR-125b-5p在乙型肝炎相关肝病患者血清中的表达及临床意义

Expression and clinical significance of serum miR-125b-5p in patients with hepatitis B related liver diseases

目的探讨miR-125b-5p在乙型肝炎相关肝病患者血清中的表达及临床意义。方法选取本院乙型肝炎相关肝病患者159例为病例组,分为慢性乙型肝炎(CHB)组40例,乙型肝炎肝硬化(HBV-LC)组65例,HBV相关性肝癌(HBV-HCC)组54例,同期选择本院健康体检人群64例为对照组,测定各组血清miR-125b-5p、ALB、ALT、AST、HBV-DNA、TBIL、TC、AFP、TG、PT水平。结果病例组ALT、AST、HBV-DNA、TBIL、PT、AFP、TC、TG水平高于对照组(P<0.05),ALB低于对照组(P<0.05);CHB组、HBV-LC组、HBV-HCC组miR-125b-5p表达水平高于对照组(P<0.05);HBV-LC组、HBV-HCC组miR-125b-5p表达水平高于CHB组(P<0.05);HBV-HCC组miR-125b-5p表达水平高于HBV-LC组(P<0.05);随着乙型肝炎相关肝病病情严重程度的增加,miR-125b-5p表达水平逐渐增加(P<0.05);miR-125b-5p与AST、ALT、TBIL、HBV-DNA、PT、AFP、TC、TG水平呈正相关(P<0.05),与ALB水平呈负相关(P<0.01);不同年龄、肿瘤最大径、肿瘤数目特征组HBV-HCC患者中血清miR-125b-5p水平相近(P> 0.05);而病理学分级越低、TNM分期越高、有淋巴血管间隙浸润、有淋巴结转移、有复发的HBV-HCC患者,血清miR-125b-5p表达水平越高(P<0.05);高水平的miR-125b-5p、HBV-DNA、AFP均为乙型肝炎相关肝病患者发生不良预后结局事件的危险因素(P<0.05);miR-125b-5p、AFP两者诊断HBV-HCC的AUC相近(P> 0.01),皆小于miR-125b-5p联合AFP诊断HBV-HCC(χ2=12.657、13.052,P<0.01)。结论血清miR-125b-5p在乙型肝炎相关肝病(CHB、HBV-LC、HBV-HCC)的表达水平升高,并与疾病进展相关;高水平的miR-125b-5p、HBV-DNA、AFP均为乙型肝炎相关肝病患者发生不良预后结局事件的危险因素;miR-125b-5p联合AFP诊断HBVHCC具有较高的灵敏度、特异度,可作为诊断HBV-HCC的生物学标志物,值得在临床上推广应用。

Objective To investigate the expression and clinical significance of serum miR-125b-5p in patients with hepatitis B related liver diseases.Methods 159 cases of hepatitis B related liver disease (case group) and 64 cases of health examinees (control group) in our hospital were selected.The case group was further divided into three subgroups according to the disease type,namely,chronic hepatitis B (CHB) group (n=40),hepatitis B virus associated liver cirrhosis (HBV-LC) group (n=65) and HBV associated hepatocellular carcinoma (HBV-HCC) group (n=54).Then the levels of miR-125b-5p,albumin (ALB),alanine aminotransferase (ALT),aspartate aminotransferase (AST),HBV-DNA,total bilirubin (TBIL),total cholesterol (TC),alpha fetoprotein (AFP),triglyceride (TG) and prothrombin time (PT) were measured in each group.Results The levels of ALT,AST,HBV-DNA,TBIL,PT,AFP,TC and TG in the case group were higher than those in the control group (P<0.05),and ALB was lower than that in the control group (P<0.05).The expression level of miR-125b-5p among all groups ranked in a descending order was HBV-HCC group,HBV-LC group,CHB group and control group (P<0.05).The expression level of miR-125b-5p was positively correlated with the disease severity (P<0.05).The miR-125b-5p expression level was positively correlated with AST,ALT,TBIL,HBV-DNA,PT,AFP,TC,TG levels (P<0.01),and was negatively correlated with ALB (P<0.01).Serum miR-125b-5p levels had no difference among patients with different age,tumor maximum diameter,and tumor number characteristics (P>0.05);The expression level of serum miR-125b-5p was positively correlated with the pathological grade,tumor node metastasis (TNM) stage,lymphatic vascular infiltration,lymph node metastasis and recurrence (P<0.05).The results showed that high levels of miR-125b-5p,HBV-DNA and AFP were risk factors for adverse prognosis outcomes in patients with hepatitis B-related liver disease (P<0.05).The AUC of miR-125b-5p and AFP were similar (P>0.01),which were all smaller than miR-125b-5p combined with AFP (χ^2=12.657,13.052,P<0.01).Conclusions Serum miR-125b-5p is elevated in hepatitis B related liver diseases,such as CHB,HBV-LC,HBV-HCC,and is associated with disease progression;High levels of miR-125b-5p,HBV-DNA,and AFP are risk factors for adverse prognosis outcomes in patients with hepatitis B-related liver disease;The sensitivity and specificity of combined detection of miR-125b-5p and AFP in the diagnosis of HBV-HCC are relatively high,so the combined detection of the two indicators can be widely applied in clinical practice.