宮頸脫落細胞miR—125b與宮頸病變關系及其在HR—HPV陽性患者分層篩查中的作用研究

NEELAMSAH 聶小鳳 張琴

摘 要：目的 比較正常宮頸、宮頸上皮內瘤變及宮頸癌患者宮頸脫落細胞中miR-125b表達水平差異，探討宮頸脫落細胞miR-125b表達水平檢測在HR-HPV陽性患者分層篩查中的作用及其與宮頸病變的關系。方法 采用第二代雜交捕獲技術進行HR-HPV初篩，HR-HPV陽性患者行宮頸液基薄層細胞學檢查及miR-125b檢測。液基細胞學檢查結果異常者直接陰道鏡下活檢行病理學檢查，液基細胞學檢查正常者行陰道鏡檢查，陰道鏡檢查下發(fā)現異常者行陰道鏡下活檢取材，余視作宮頸組織學正常，不做宮頸活檢。RT-qPCR檢測正常宮頸及不同級別宮頸病變中miR-125b表達水平，比較不同組織學分組之間的宮頸脫落細胞miR-125b表達水平，繪制ROC曲線，探討miR-125b、液基細胞學檢查在宮頸病變中的診斷作用。結果 宮頸脫落細胞miR-125b水平隨著宮頸病變程度加重逐漸升高（P<0.05）；在HR-HPV陽性患者分層篩查中，宮頸液基細胞學診斷宮頸高級別上皮內病變的敏感性、特異性分別為64.90%、80.70%，AUC為0.728（95%CI：0.657～0.779，P<0.001）。與液基細胞學檢查相比，宮頸脫落細胞miR-125b檢測診斷宮頸高級別上皮內病變的靈敏性、特異性更高（87.30% vs 64.90%；69.20% vs 80.70%），AUC為 0.864（95%CI：0.800～0.928，P<0.001）。結論 miR-125b水平隨著宮頸病變加重逐漸升高，檢測宮頸脫落細胞miR-125b水平可有效分流HR-HPV陽性患者，敏感性高于細胞學檢查，可能成為一種有效的分層篩查方法。

關鍵詞：宮頸病變；miR-125b；HR-HPV；宮頸癌篩查

中圖分類號：RR737.33 文獻標識碼：A DOI：10.3969/j.issn.1006-1959.2018.23.021

文章編號：1006-1959（2018）23-0076-04

Abstract：Objective To compare the expression levels of miR-125b in cervical exfoliated cells of normal cervix， cervical intraepithelial neoplasia and cervical cancer， and to explore the role of miR-125b expression in cervical exfoliated cells in stratified screening of HR-HPV positive patients. The relationship between cervical lesions. Methods The second-generation hybridization capture technique was used for HR-HPV screening. The HR-HPV-positive patients underwent cervical-based thin-layer cytology and miRNA125b detection. The results of liquid-based cytology were abnormal. The pathological examination was performed directly under biopsy. The liquid-based cytology was performed by colposcopy. The abnormalities were found under colposcopy. The colposcopy biopsy was performed. Normal， no cervical biopsy. RT-qPCR was used to detect the expression of miR-125b in normal cervical and different grades of cervical lesions. The expression levels of miR-125b in cervical exfoliated cells were compared between different histological groups. ROC curves were drawn to investigate miR-125b and liquid-based cytology. The role of diagnosis in cervical lesions. Results The level of miR-125b in cervical exfoliated cells increased with the severity of cervical lesions （P<0.05）. In the stratified screening of HR-HPV positive patients， the sensitivity of cervical liquid-based cytology in the diagnosis of high-grade intraepithelial lesions of the cervix， The specificities were 64.90% and 80.70%， respectively， and the AUC was 0.728 （95% CI： 0.657～0.779，P<0.001）. Compared with liquid-based cytology， the sensitivity and specificity of cervical exfoliated cells miR-125b for the diagnosis of high-grade intraepithelial lesions of the cervix were higher （87.30% vs 64.90%； 69.20% vs 80.70%）， and the AUC was 0.864 （95%CI： 0.800～0.928，P<0.001）. Conclusion The level of miR-125b is gradually increased with the increase of cervical lesions. The detection of miR-125b in cervical exfoliated cells can effectively divert HR-HPV positive patients， which is more sensitive than cytology and may be an effective stratified screening method.

Key words：Cervical lesions；miR-125b；HR-HPV；Cervical cancer screening

宮頸癌（cervical cancer，CC）是發(fā)展中國家女性常見的惡性腫瘤，發(fā)病率高且逐年上升[1]，其發(fā)生一般需經歷從正常宮頸上皮到不同級別癌前病變的演變過程，平均需5～20年[2]。宮頸癌雖發(fā)病率高但其病程進展緩慢，加之宮頸位置易于被暴露和取材，因此是目前唯一可以通過篩查降低浸潤癌發(fā)生率的惡性腫瘤。宮頸上皮內瘤變（CIN）是宮頸癌前病變，通過篩查及時發(fā)現宮頸上皮內瘤變，及時治療，是預防宮頸癌的有效措施。高危型人乳頭瘤病毒（HR-HPV）檢測和宮頸細胞學檢查是目前最主要的兩種宮頸癌篩查方法。……