尿液外泌体长链非编码RNA MALAT1和HIF1A-AS2对膀胱癌诊断的价值

Diagnostic value of urine exosomes long non-coding RNA MALAT1 and HIF1A-AS2 in bladder cancer

目的 检测膀胱癌患者尿液外泌体中人肺腺癌转移相关转录因子1 (MALAT-1)和缺氧诱导因子1α反义RNA2(HIF1A-AS2)的表达水平,分析其与患者临床病理参数的关系,探讨其在膀胱癌诊断中的临床应用价值。方法 收集2019年1月至2020年12月于西安医学院第一附属医院就诊的膀胱癌、膀胱良性疾病患者及健康人各40例尿液样本,采用ELISA法检测各组尿液外泌体中MALAT1和HIF1A-AS2的表达水平。进一步分析其与膀胱癌患者临床病理参数的相关性;绘制ROC曲线并分析MALAT1和HIF1A-AS2对膀胱癌的诊断价值。结果 膀胱癌组中MALAT1和HIF1A-AS2的表达水平显著高于膀胱良性疾病和健康人对照组,差异具有统计学意义(P<0.05);MALAT1和HIF1A-AS2的表达水平与膀胱癌患者的病理分级和分期的差异无统计学意义(P>0.05),而与肿瘤的大小密切相关(P<0.05);尿液外泌体中MALAT1诊断膀胱癌的曲线下面积(AUC^(ROC))为0.748,敏感性为75.0%,特异性为66.25%;HIF1A-AS2诊断膀胱癌的AUC^(ROC)为0.757,敏感性为75.0%,特异性为68.75%;MALAT1和HIF1A-AS2联合检测诊断膀胱癌的AUC^(ROC)为0.820,敏感性为85.0%,特异性为81.25%,均高于两项指标的单独诊断价值。结论 尿液外泌体中高表达的MALAT1和HIF1A-AS2可作为膀胱癌诊断的潜在生物学标志物。

Objective To detect the expression levels of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)and hypoxia-inducible factor 1 alpha antisense RNA 2(HIF1A-AS2)in urine exosomes of patients with bladder cancer,analyze their correlations with clinicopathological parameters,and investigate their diagnostic value in bladder cancer.Methods The expression levels of MALAT1 and HIF1A-AS2 in urine exosomes of 40 patients with bladder cancer,40 patients with benign bladder diseases and 40 healthy persons from the First Affiliated Hospital of Xi'an Medical University during January 2019 and December 2020 were detected by an enzyme linked immunosorbent assay(ELISA),and their correlations with clinicopathological parameters of bladder cancer patients were analyzed.The receiver operating characteristic(ROC)curve was drawn,and the diagnostic value of MALAT1 and HIF1A-AS2 in bladder cancer was analyzed.Results The expression levels of MALAT1 and HIF1A-AS2 in bladder cancer patients were significantly higher than those in patients with benign bladder diseases and healthy controls(P<0.05).The expression levels of MALAT1 and HIF1A-AS2 were not correlated with pathological grading and staging of patients with bladder cancer(P>0.05),but were closely related to the size of tumor(P<0.05).The area under the ROC curve(AUC^(ROC)),sensitivity and specificity of MALAT1 in urine exosomes for the diagnosis of bladder cancer were 0.748,75.0%and 66.25%,respectively,and those of HIF1A-AS2 were 0.757,75.0%and 68.75%,respectively.The AUC^(ROC),sensitivity and specificity of the combined detection of MALAT1 and HIF1A-AS2 were 0.820,85.0%and 81.25%,respectively,which was higher than those of the two separate indicators.Conclusion MALAT1 and HIF1A-AS2,which are highly expressed in urine exosomes,may be used as potential biomarkers for the diagnosis of bladder cancer.