血清miR-17-92簇在HPV阳性宫颈癌中的早期诊断价值

The value of serum miR-17-92 cluster in early diagnosis of HPV-positive cervical cancer

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 levels of miR-17-92 cluster （miR-17, miR-18a, miR-19a, miR-19b, miR-20a and miR-92a） in the serum from patients with cervical cancer （CC） and cervical intraepithelial neoplasia （CIN）, and to evaluate their clinical significance in the early diagnosis of human papillomavirus （HPV） positive cervi- cal cancer. Methods Serum samples were collected from 150 HPV positive CC patients （cancer group）, 100 HPV- positive patients with CIN1-3 （ CIN group） and 50 HPV-positive women without malignant disease （ control group）. RT-qPCR was performed to analyze the expression levels of serum miR-17-92 cluster. The diagnostic values of the dif- ferently expressed miRNAs were evaluated and compared with Thinprep cytologic test （TCT）. Results The expression of serum miR-18a and miR-92a were significantly higher in CC group than in CIN group and control group; the expres- sion of serum miR-18a and miR-92a were significantly higher in CIN group than in control group; the expression of miR-18a was significantly higher in CIN1-2 patients than in control group （all P 〈 0.05 ）. Receiver operating character- istic （ROC） curve analysis revealed that the area under the curve （AUC） of serum miR-18a, miR-92a and TCT for identifying CIN3 and CC （ CIN3 ＋ ） was 0.792 （95% CI： O. 749-0.862 ; sensitivity： 87% ; specificity： 65% ）, 0.799 （95% CI： 0.744-0. 847; sensitivity： 55.8% ; specificity： 92% ） and 0. 645 （95% CI： O. 582-0. 704; sensitivity： 51.9% ; specificity： 77% ）, respectively. Compared with TCT, detection of serum miR-18a and miR-92a achieved higher performance efficiency for identifying CIN3 ＋ （ all P 〈 0.01 ）. Conclusion MiR-18a and miR-92a, the mem- bers of miR-17-92 cluster, are highly expressed in the serum of HPV-positive patients with cervical cancer, and could serve as potential biomarkers for early diagnosis of cervical neoplasia and high-grade CIN identification.