目的 分析PAX1基因甲基化与HPV-DNA分型检测在宫颈癌前病变诊疗中的特征及潜在关联。方法 选择2021-06至2022-03在解放军总医院第三医学中心妇产科行液基薄层细胞检测(TCT)和人乳头瘤病毒-DNA(HPV-DNA)分型检测的患者。纳入研究TCT结果异常,意义不明的非典型鳞状细胞(ASCUS)和(或)HR-HPV阳性患者194例,宫颈组织病变筛查结果异常并转诊阴道镜下取病理活检的患者共130例。所有患者进行TCT、HPV-DNA分型检测、定量PAX1基因甲基化检测。结果 CIN3+(CIN3和宫颈癌)患者的PAX1基因甲基化数值显著高于正常、CIN1、CIN2患者,按照活检病理级别从高到低PAX1基因甲基化数值依次分别为18.21(17.56,18.66)和20.5(20.07,20.80),20.41(20.19,20.72),20.21(19.77,20.42);TCT结果提示ASCUS的患者共45例,CIN2+(CIN2、CIN3和宫颈癌)PAX1基因甲基化数值显著高于正常/CIN1,按照活检病理级别从高到低PAX1基因甲基化数值依次分别为 18.87(17.80,20.26)和 20.51(20.19,20.73);HPV16、18阳性患者的PAX1基因甲基化数值均显著高于非HPV16/18阳性患者,HPV16阳性和高危型非HPV16/18阳性患者PAX1基因甲基化数值分别为19.10(17.97,19.88)和20.33(20.00,20.50),HPV18阳性和非HPV16/18阳性患者PAX1基因甲基化水平分别为19.49(18.65,20.31)和20.33(20.00,20.50)。但单一HPV16阳性与单一HPV18阳性患者的PAX1基因甲基化数值相比,二者间的数值则无统计学差异。结论 PAX1基因甲基化检测有助于早期识别CIN3+和ASCUS宫颈高级别病变,也有助于降低ASCUS患者的阴道镜转诊率。
Abstract
Objective To analyze the characteristics and potential correlation between PAX1 gene methylation and HPV-DNA typing in the diagnosis and treatment of cervical precancerous lesions. Methods Patients who underwent liquid-based thin-layer cell testing (TCT) and human papillomavirus DNA (HPV-DNA) typing in the Department of Obstetrics and Gynecology of the Third Medical Center of PLA General Hospital from June 2021 to March 2022 were selected. A total of 194 patients with abnormal TCT results≥ atypical squamous cells of unknown significance (ASCUS) and/or HR-HPV positive and 130 patients with abnormal cervical tissue screening results who were referred for colposcopic biopsy were included in this study. TCT, HPV-DNA typing and quantitative PAX1 gene methylation were performed in all patients. Results Compared with CIN3+ (CIN3 and cervical cancer) and normal/cervicitis, CIN1 and CIN2, the methylation value of PAX1 gene in CIN3+ patients was significantly higher than that in normal, CIN1 and CIN2 patients. The methylation values of PAX1 gene from high to low were 18.21 (17.56, 18.66), 20.5 (20.07, 20.80), 20.41 (20.19, 20.72), 20.21 (19.77, 20,42), respectively. The TCT results showed that there were 45 patients with ASCUS, CIN2+ (CIN2, CIN3 and cervical cancer) compared with normal/CIN1, and the methylation value of PAX1 gene CIN2+ was significantly higher than that of normal/CIN1. The methylation values of PAX1 gene from high to low were 18.87 (17.80, 20.26) and 20.51 (20.19, 20.73), respectively. The methylation values of PAX1 gene in HPV16 and 18 positive patients were significantly higher than those in non-HPV16/18 positive patients. The methylation values of PAX1 gene in HPV16 positive and high-risk non-HPV16/18 positive patients were 19.10 (17.97, 19.88) and 20.33 (20.00, 20.50), respectively. The methylation levels of PAX1 gene in HPV18-positive and non-HPV16/18 positive patients were 19.49 (18.65, 20.31) and 20.33 (20.00, 20.50), respectively. However, there was no significant difference in the methylation value of PAX1 gene between single HPV16 positive patients and single HPV18 positive patients). Conclusions The methylation of PAX1 gene is related with the progression of cervical lesions and the type of HPV infection. The methylation values of PAX1 gene in patients with single HPV16 positive and single HPV18 positive are significantly higher than those in patients without HPV16/18 positive. In ASCUS patients, the methylation value of PAX1 gene in CIN2+ is significantly higher than that in normal /CIN1. It is suggested that PAX1 gene methylation detection is helpful for early identification of CIN3+ and ASCUS cervical high-grade lesions, and also helps to reduce the colposcopy referral rate of ASCUS patients.
关键词
PAX1基因甲基化检测 /
人类乳头状病毒 /
DNA分型 /
宫颈病变
Key words
PAX1 methylation detection /
human papillomavirus /
DNA /
cervical lesions
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基金
首都科研发展专项项目(2020-1-5112)
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