血清miR-9和miR-155表达在HPV阳性宫颈癌诊断和预后中的临床价值

Clinical significance of serum miR-9 and miR-155 expression in diagnosis and prognosis of HPV-positive cervical cancer

目的研究血清miR-9和miR-155表达在人类乳头瘤病毒(HPV)阳性宫颈癌诊断和预后中的临床价值。方法HPV阳性的宫颈癌患者119例为宫颈癌组,同期就诊HPV阳性子宫内瘤变(CIN)的患者75例和HPV阳性良性宫颈病变或者单纯HPV阳性者45例分为为CIN组和对照组。采用实时定量PCR方法检测3组血清miR-9和miR-155表达量。观察宫颈癌患者血清miR-9和miR-155表达与临床指标和诊断宫颈癌的临床价值,比较血清miR-9和miR-155表达水平与宫颈癌死亡的关系及评价死亡的临床价值。结果宫颈癌组的血清miR-9和miR-155表达明显高于CIN组和对照组(P<0.01),而CIN组的表达水平明显高于对照组(P<0.01)。血清miR-9和miR-155表达水平在诊断宫颈癌方面具有较高的灵敏度和特异性,联合检测的曲线下面积为0.909,灵敏度为82.4%,特异度82.7%,在诊断宫颈癌方面明显优于单独miR-9(Z=2.864,P=0.004)和miR-155(Z=4.156,P=0.000),而两个指标之间的曲线下面积差异无统计学意义(P>0.05)。宫颈癌患者血清miR-9和miR-155表达与年龄,病理分型,分化程度和肿瘤直径无明显相关性(P>0.05),而与临床分期,淋巴转移,间质浸润深度,累及阴道壁,累及宫旁组织和累及血管间隙具有明显相关性(P<0.01)。宫颈癌死亡组血清miR-9和miR-155表达水平明显高于生存组(P<0.01)。血清miR-9和miR-155表达水平在预测宫颈癌死亡方面具有较高的灵敏度和特异性,联合检测的曲线下面积为0.958,灵敏度为97.0%,特异度87.2%,在预测死亡方面明显优于单独miR-9(Z=2.376,P=0.018)和miR-155(Z=2.048,P=0.041),而两个指标之间的曲线下面积差异无统计学意义(P>0.05)。结论miR-9和miR-155基因参与了HPV阳性宫颈癌的发生发展,其在宫颈癌诊断和预后的判断具有重要的临床价值。

Objective To investigate the clinical significance of serum miR-9 and miR-155 expression in diagnosis and prognosis of human papillomavirus(HPV)positive cervical cancer.Methods A total of 119 HPV-positive patients with cervical cancer who were treated in our hospital from January 2015 to December 2017 were enrolled as cervical cancer group,and the other 75 patients with HPV-positive intrauterine neoplasia(CIN)and 45 patients with HPV-positive benign cervical lesions or HPV-positive people were enrolled as CIN group and control group,respectively.Real-time quantitative PCR was used to detect the expression levels of serum miR-9 and miR-155.Moreover the correlation between the expression of serum miR-9,miR-155 and the diagnosis of cervical cancer was observed,and the correlation between the expression of serum miR-9,miR-155 and the death of cervical cancer was also observed.Results The expression levels of serum miR-9 and miR-155 in cervical cancer group were significantly higher than those in CIN group and control group(P<0.01),and the expression levels in CIN group were significantly higher than those in control group(P<0.01).The expression levels of serum miR-9 and miR-155 had high sensitivity and specificity in diagnosis of cervical cancer.The area under the curve of combination detection was 0.909,the sensitivity was 82.4%,and the specificity was 82.7%,which was significantly better than that by simple miR-9 detection and simple miR-155 detection(P<0.01),however,there was no significant difference in the area under the curve between the two indexes(P>0.05).There was no significant correlation between the expression of serum miR-9,miR-155 and patient’s age,pathological type,degree of differentiation and tumor diameter(P>0.05),however,which was closely correlated with clinical stage,lymphatic metastasis,depth of interstitial infiltration,involvement of vaginal wall,involved parametrial tissue and involved vascular space(P<0.01).The expression levels of serum miR-9 and miR-155 in death cae group were significantly higher than those in survival case group(P<0.01).The serum levels of miR-9 and miR-155 had high sensitivity and specificity in predicting cervical cancer death.The area under the curve of combination detection was 0.958,the sensitivity was 97.0%,and the specificity was 87.2%,which was superior to that by simple miR-9 detection and simple miR-155 detection in predicting cervical cancer death(P<0.01),however,there was no significant difference in the area underthe curve between the two indexes(P>0.05).Conclusion The miR-9 and miR-155 genes areinvolved in the pathogenesis and development ofHPV-positive cervical cancer,which have important clinical value in the diagnosis and prognosis evaluation of cervical cancer.