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目的检测miR-17-92簇成员分子(miR-17、miR-18a、miR-19a、miR-19b、miR-20a和miR-92a)在人乳头瘤病毒(HPV)阳性宫颈癌(CC)及上皮内瘤变(CIN)患者血清中的表达水平,并评估其对HPV阳性宫颈癌的早期诊断价值。方法收集HPV阳性宫颈癌患者150例(CC组)、HPV阳性CIN1~3级患者100例(CIN组)及单纯HPV阳性或子宫良性病变者150例(对照组)血清,采用实时定量PCR(RT-q PCR)法检测血清中miR-17-92簇成员分子的表达,结合液基薄层细胞学检测(TCT)结果,评价miR-17-92簇成员分子在HPV阳性宫颈癌中的早期诊断价值。结果与对照组相比,miR-18a和miR-92a在CC组血清中异常高表达,且其表达水平显著高于CIN组及对照组,两者在CIN3级患者中的表达水平及miR-18a在CIN1-2级患者中的表达水平均显著高于对照组(P均<0.05)。受试者工作曲线(ROC曲线)分析结果显示,血清miR-18a诊断CIN3及CC(CIN3+)的曲线下面积(AUC)为0.792(95%CI:0.749~0.862),灵敏度为87%,特异度为65%;血清miR-92a诊断CIN3+的AUC为0.799(95%CI:0.744~0.847),灵敏度为55.8%,特异度为92%;TCT诊断CIN3+的AUC为0.645(95%CI:0.582~0.704),灵敏度为51.9%,特异度为77%。血清miR-18a和miR-92对宫颈癌和CIN3+的诊断效能均显著优于TCT检测(P均<0.01)。结论 miR-17-92簇成员分子miR-92a和miR-18a在HPV阳性宫颈癌患者血清中高表达,并可作为HPV阳性宫颈癌的早期诊断及鉴别高级别CIN的潜在标志物。
Objective To detect the expression of miR-17-92 cluster members (miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a) in human papillomavirus The level of serum in patients with intraepithelial neoplasia (CIN) was assessed and its diagnostic value for HPV-positive cervical cancer was evaluated. Methods One hundred and seventy patients with HPV positive cervical cancer (CC group), 100 patients with HPV positive CIN1 ~ 3 (CIN group) and 150 patients with HPV positive or benign uterine lesions (control group) were collected and analyzed by real - time PCR qPCR method was used to detect the expression of miR-17-92 cluster members in serum and combined with the results of liquid-based TLCT to evaluate the early diagnosis of HPV-17-92 cluster members in HPV-positive cervical cancer value. Results Compared with the control group, miR-18a and miR-92a were highly expressed in the serum of CC group, and the expression levels of miR-18a and miR-92a were significantly higher than that of CIN group and control group The expression levels in CIN1-2 patients were significantly higher than those in control group (all P <0.05). The receiver operating curve (ROC curve) analysis showed that the area under the curve (AUC) of serum miR-18a for CIN3 and CC (CIN3 +) was 0.792 (95% CI: 0.749-0.862) with a sensitivity of 87% (95% CI: 0.744-0.847). The sensitivity and specificity of miR-92a for CIN3 + were 0.799 (55% CI: 0.582-0.704) ), With a sensitivity of 51.9% and a specificity of 77%. The diagnostic efficacy of serum miR-18a and miR-92 on cervical cancer and CIN3 + were significantly better than that of TCT (all P <0.01). Conclusion miR-92a and miR-18a, a member of miR-17-92 cluster, are highly expressed in the serum of patients with HPV-positive cervical cancer and may be potential markers for early diagnosis of HPV-positive cervical cancer and differential diagnosis of high-grade CIN.