病毒学报

目的 探究miR-21、miR-199及miR-18a在高危型人乳头瘤病毒（High-risk human papillomavirus,HR-HPV）感染宫颈癌组织中的表达及诊断价值。方法 选取HR-HPV感染宫颈癌患者82例（宫颈癌组）、HR-HPV感染宫颈上皮内瘤变（Cervical intraepithelial neoplasia,CIN）患者60例（CIN组）及HR-HPV阴性正常宫颈组织40例（正常对照组），采用RT-PCR检测三者相对表达量，分析其与临床病理特征的关联及联合诊断价值。结果 宫颈癌组miR-21(2.86±0.72)、miR-18a(3.12±0.85)表达显著高于CIN组及正常对照组，miR-199(0.42±0.15)显著低于后两组（P<0.001）。三者表达与宫颈癌临床分期、病理分化、淋巴结转移及HPV16/18感染相关（P<0.05），且miR-21与miR-18a呈正相关，二者均与miR-199呈负相关（P<0.001）。联合检测诊断宫颈癌的AUC为0.92(95%CI:0.87～0.96)，优于单一指标（P<0.05）。结论 HR-HPV感染宫颈癌组织中miR-21、miR-18a高表达、miR-199低表达，与疾病进展及HPV分型相关，联合检测可作为潜在分子诊断标志物。

Objective To explore the expression and diagnostic value of miR-21,miR-199,and miR-18a in cervical cancer tissues infected with high-risk human papillomavirus(HR-HPV).Methods A total of 82cervical cancer patients with HR-HPV infection(cervical cancer group),60 patients with HR-HPV-infected cervical intraepithelial neoplasia(CIN group),and 40 cases of HR-HPV-negative normal cervical tissues(normal control group) were selected.Quantitative real-time polymerase chain reaction(RT-PCR) was used to detect the relative expression levels of the three microRNAs,and their associations with clinicopathological features and combined diagnostic value were analyzed.Results The expressions of miR-21(2.86±0.72) and miR-18a(3.12±0.85) in the cervical cancer group were significantly higher than those in the CIN group and normal control group,while miR-199(0.42±0.15) was significantly lower(P<0.001).The expressions of the three microRNAs were correlated with clinical stage,pathological differentiation,lymph node metastasis,and HPV16/18 infection of cervical cancer(P<0.05).miR-21 was positively correlated with miR-18a,and both were negatively correlated with miR-199(P<0.001).The area under the receiver operating characteristic(ROC) curve(AUC) of the combined detection for diagnosing cervical cancer was 0.92(95%CI:0.87～0.96),which was superior to that of single indicators(P<0.05).Conclusion High expressions of miR-21 and miR-18a and low expression of miR-199 exist in HR-HPV-infected cervical cancer tissues,which are related to disease progression and HPV typing.Combined detection of these three microRNAs can serve as potential molecular diagnostic markers for cervical cancer.