郭艳平 杨青 王诗睿 李思敏 于博阳 杨筱凤

摘要：目的 探讨SOX1和PAX1基因甲基化检测对宫颈高级别病变二次分流的价值。方法 采集122例人乳头瘤病毒（HPV）阳性患者的宫颈脱落细胞，同时行液基薄层细胞学检查（TCT）和SOX1/PAX1基因甲基化检测。结果 HPV联合TCT检测对宫颈上皮内瘤变（CIN）2级及以上（CIN2+）检出灵敏度为95.24%，特异度为23.75%。结合SOX1/PAX1基因甲基化检测二次分流后，对CIN2+检出灵敏度为83.33%，与HPV联合TCT检测差异无统计学意义（P=0.078）；特异度为77.50%，明显高于HPV联合TCT检测（P<0.001）。CIN2+组SOX1/PAX1基因甲基化水平高于正常宫颈组织及CIN1组（P<0.001）。SOX1、PAX1基因甲基化对CIN2+诊断的截断值分别为-11.81、-11.98。结论 SOX1/PAX1基因甲基化检测二次分流后，CIN2+检出的效能和准确性明显提升。

关键词：SOX1；PAX1；甲基化；宫颈病变

中图分类号： R711  文献标识码： A  文章编号：1000-503X（2024）03-0329-05

DOI：10.3881/j.issn.1000-503X.15734

Value of SOX1 and PAX1 Gene Methylation Detection in Secondary Triage of High-Grade Cervical Lesions

GUO Yanping，YANG Qing，WANG Shirui，LI Simin，YU Boyang，YANG Xiaofeng

Department of Obstetrics and Gynecology，The First Affiliated Hospital of Xian Jiaotong University，Xian 71006 China

Corresponding author：YANG Xiaofeng Tel：029-85323844，E-mail：yxf73@163.com

ABSTRACT：Objective To evaluate the value of SOX1 and PAX1 gene methylation detection in the secondary triage of high-grade cervical lesions.Methods Exfoliated cervical cells were collected from 122 patients tested positive for human papilloma virus （HPV） and subjected to thin-prep cytologic test （TCT） and SOX1/PAX1 gene methylation tests.Results The HPV test combined with TCT showed the sensitivity of 95.24% and the specificity of 23.75% for detecting cervical intraepithelial neoplasia （CIN） grade 2 and above （CIN2+）.After the addition of the SOX1/PAX1 gene methylation detection in secondary triage，the sensitivity for detecting CIN2+ was 83.33%，which had no statistically significant difference from the sensitivity of TCT combined with HPV test （P=0.078）.However，the specificity reached 77.50%，which was significantly higher than that of HPV test combined with TCT （P<0.001）.The SOX1/PAX1 gene methylation level in the CIN2+ group was higher than those in the normal cervical tissue and the CIN1 group（P<0.001）.The cut-off values of SOX1 and PAX1 gene methylation for CIN2+ detection were -11.81 and -11.98，respectively.Conclusion Adding the detection of SOX1/PAX1 gene methylation in secondary triage significantly improves the efficiency and accuracy of CIN2+ detection.

Key words：SOX1；PAX1；methylation；cervical lesion

Acta Acad Med Sin，2024，46（3）：329-333

宫颈癌发病率在女性生殖系统恶性肿瘤中居首位，我国宫颈癌每年新发病例11.93万，死亡病例3.72万［1］。高危型人乳头瘤病毒（human papilloma virus，HPV）持续感染是导致宫颈上皮内瘤变（cervical intraepithelial neoplasia，CIN）及宫颈癌的主要因素［2］。目前HPV检测是我国宫颈癌筛查的主要方法，但其存在敏感度高而特异度不足的问题［3］，易导致过度的阴道镜检查及不必要的有创检查。因此，探索精细化的危险分层方法是平衡宫颈癌筛查中风险和获益的新目标。表观遗传学在肿瘤的发生发展中发挥着重要作用，其主要通过DNA甲基化、组蛋白修饰、非编码RNA调控和染色质结构重构等方式改变基因功能和表达水平，进而影响肿瘤的进展［4］。研究发现，宫颈癌患者肿瘤抑制因子、转录因子和细胞周期调节因子基因的启动子区发生甲基化，导致抑癌基因功能失活和转录抑制，从而促进宫颈癌的侵袭和转移［5］。SOX1基因是Y染色体性别决定区相关基因家族成员，参与胚胎发育和凋亡过程中转录因子的编码，SOX1基因甲基化水平在宫颈癌组织中显著上调［6］。……