宫颈组织HPV E6/E7 mRNA Atg-12 Tie-1表达情况与鳞状上皮内病变病理分级的相关性

目的 探讨宫颈组织人类乳头瘤病毒(HPV)E6/E7 mRNA、自噬相关蛋白-12(Atg-12)、酪氨酸激酶受体-1(Tie-1)表达情况与鳞状上皮内病变(SIL)病理分级的相关性。方法 选取2020年5月至2021年10月新乡市中心医院病理科诊断为SIL的患者227例,根据宫颈病变分级分为低级别鳞状上皮内病变(LSIL)组124例和高级别鳞状上皮内病变(HSIL)组103例,另选取子宫肌瘤手术患者80例为对照组。所有患者均采用支链DNA信号扩增法检测HPV E6/E7 mRNA,采用免疫组化法及免疫印迹法检测Atg-12、Tie-1蛋白。分析E6/E7 mRNA、Atg-12、Tie-1与病理分级的相关性,绘制受试者特征(ROC)曲线分析各指标对HSIL与LSIL的鉴别诊断价值。结果 HSIL组的HPV E6/E7 mRNA、Tie-1蛋白阳性检出率高于LSIL组和对照组(P<0.05),HSIL组的Atg-12蛋白阳性检出率低于LSIL组和对照组(P<0.05),HSIL组的HPV E6/E7 mRNA拷贝数、Tie-1蛋白表达量高于LSIL组和对照组(P<0.05),HSIL组的Atg-12蛋白表达量低于LSIL组和对照组(P<0.05)。HPV E6/E7 mRNA、Tie-1蛋白表达量与SIL病理分级呈正相关(r=0.514,0.488),Atg-12蛋白表达量与SIL病理分级呈负相关(r=-0.433)。HPV E6/E7 mRNA、Atg-12、Tie-1鉴别诊断HSIL与LSIL的灵敏度为88.57%、74.29%、82.86%,特异度为57.14%、66.67%、64.29%。3项指标联合诊断的灵敏度为77.14%,特异度为85.71%(AUC=0.854)。结论 HSIL患者HPV E6/E7 mRNA、Tie-1表达较高,Atg-12表达较低。HPV E6/E7 mRNA、Atg-12、Tie-1表达与SIL病理分级有一定相关性,联合诊断可为HSIL与LSIL的鉴别诊断提供参考。

Correlation between HPV E6/E7 mRNA, Atg-12 and Tie-1 in cervical tissues and pathological grading of squamous intraepithelial lesions

Objective To explore the correlation between human papillomavirus (HPV) E6/E7 mRNA, autophagy-related protein-12 (Atg-12) and tyrosine kinase receptor-1 (Tie-1) in cervical tissues and pathological grading of squamous intraepithelial lesion (SIL). Methods A total of 227 patients confirmed with SIL in the Pathology Department of Xinxiang Central Hospital were enrolled between May 2020 and October 2021. According to cervical lesion grading, they were divided into low-grade squamous intraepithelial lesion (LSIL) group (124 cases) and high-grade squamous intraepithelial lesion (HSIL) group (103 cases). A total of 80 patients undergoing uterine fibroid surgery were enrolled as control group. HPV E6/E7 mRNA was detected by branched-strand DNA signal amplification method. Atg-12 and Tie-1 were detected by immunohistochemistry and Western blot. The correlation between E6/E7 mRNA, Atg-12, Tie-1 and pathological grading was analyzed. And their value in the differential diagnosis of HSIL and LSIL was analyzed by ROC curves. Results The positive detection rates of HPV E6/E7 mRNA and Tie-1 in HSIL group were higher than those in LSIL group and control group (P<0.05), while the positive detection rate of Atg-12 was lower than that in LSIL group and control group (P<0.05). The copy value of HPV E6/E7 mRNA and Tie-1 expression in HSIL group was higher than that in LSIL group and control group (P<0.05), while Atg-12 expression was lower than that in LSIL group and control group (P<0.05). The expressions of HPV E6/E7 mRNA and Tie-1 were positively correlated with the pathological grading of SIL (r=0.514, r=0.488), while Atg-12 expression was negatively correlated with it (r=-0.433). The sensitivity and specificity of HPV E6/E7 mRNA, Atg-12 and Tie-1 in the differential diagnosis of HSIL and LSIL was (88.57%, 74.29%, 82.86%) and (57.14%, 66.67%, 64.29%), respectively. The sensitivity and specificity of the combined diagnosis of the three indexes was 77.14% and 85.71%, respectively (AUC=0.854). Conclusions The expressions of HPV E6/E7 mRNA and Tie-1 are up-regulated, while Atg-12 expression is down-regulated in HSIL patients. HPV E6/E7 mRNA, Atg-12 and Tie-1 are related to the pathological grading of SIL. The combined diagnosis can provide reference for the differential diagnosis of HSIL and LSIL.