2025 年第 10 期 第 20 卷

原钙黏蛋白α4基因甲基化检测在宫颈癌筛查中的价值

The value of protocadherin alpha 4 gene methylation detection in cervical cancer screening

作者：王娟娟吴雯婷罗婷荣婷婷

英文作者：Wang Juanjuan Wu Wenting Luo Ting Rong Tingting

单位：上海交通大学医学院附属新华医院检验科,上海200092

英文单位：Department of Laboratory Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 200092 China

关键词：宫颈癌；原钙黏蛋白α4基因；甲基化特异性聚合酶链反应；宫颈脱落细胞；高危型人乳头瘤病毒

英文关键词：Cervicalcancer;Protocadherinalpha4gene;Methylation-specificpolymerasechainreaction; Cervicalexfoliatedcells;High-riskhumanpapillomavirus

• 摘要：

• 目的 探讨原钙黏蛋白α4(PCDHA4)基因甲基化检测在宫颈癌筛查中的价值，为宫颈癌的早期诊断提供新的方法和依据。方法 收集2019年9月至2024年6月在上海交通大学医学院附属新华医院妇科就诊的186例女性患者［包括宫颈上皮内瘤变(CIN)1级90例（CIN 1组），CIN 2级34例（CIN 2组），CIN 3级28例（CIN 3组），宫颈癌34例（宫颈癌组）］及52名健康体检女性(对照组)的宫颈脱落细胞，提取基因组DNA进行人乳头瘤病毒（HPV）检测及PCDHA4基因甲基化特异性聚合酶链反应检测，分析PCDHA4基因甲基化检测在宫颈癌或癌前病变中的诊断性能。结果 CIN 3组及宫颈癌组中PCDHA4基因甲基化阳性率明显高于CIN 2组、CIN 1组和对照组［89.3%（25/28）、94.1%（32/34）比61.8%（21/34）、36.7%（33/90）、40.4%（21/52）］(均P＜0.05)。CIN 2组、CIN 3组及宫颈癌组中PCDHA4 ΔCt明显小于CIN 1组和对照组(均P＜0.05)。PCDHA4 ΔCt（截断值为6.34时，敏感度为64.6%，特异度为91.5%）用于诊断CIN 2级及以上病变的性能明显优于液基薄层细胞检测(TCT)、HPV16/18、高危型HPV（hrHPV）和PCDHA4（均P＜0.05)，PCDHA4 ΔCt（截断值为5.45时，敏感度为74.2%，特异度为92.6%）用于诊断CIN 3级及以上病变的性能也显著优于TCT、HPV16/18、hrHPV和PCDHA4（均P＜0.05)。与TCT相比，PCDHA4 ΔCt用于非16/18型hrHPV阳性女性CIN 2级及以上或CIN 3级及以上分流时具有更好的性能（均P＜0.05）。结论 PCDHA4基因甲基化检测可作为宫颈癌筛查的潜在生物标志物，有助于hrHPV阳性人群的分流，对宫颈癌的早期诊断具有重要意义。

• Objective To investigate the value of protocadherin alpha 4 (PCDHA4) gene methylation detection in cervical cancer screening, and to provide a new method and basis for the early diagnosis of cervical cancer. Methods From September 2019 to June 2024, the cervical exfoliated cells of 186 female patients ［included 90 cases of cervical intraepithelial neoplasia (CIN) grade 1 (CIN 1 group), 34 cases of CIN grade 2 (CIN 2 group), 28 cases of CIN grade 3 (CIN 3 group), and 34 cases of cervical cancer (cervical cancer group)］ and 52 healthy women (control group) who were treated in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were collected. Then the genomic DNA was extracted for human papilloma virus (HPV) detection and PCDHA4 gene methylation-specific PCR detection, and the diagnostic performance of PCDHA4 gene methylation detection in cervical cancer or precancerous lesions was analyzed. Results The positive rate of PCDHA4 gene methylation in CIN 3 and cervical cancer was significantly higher than that in CIN 2, CIN 1 and control group ［89.3%(25/28), 94.1%(32/34) vs 61.8%(21/34), 36.7%(33/90), 40.4%(21/52)］, and the differences between the groups were statistically significant (all P＜0.05). The PCDHA4 ΔCt in CIN 2, CIN 3 and cervical cancer group was significantly lower than that in CIN 1 and control group, and the difference between groups was statistically significant (all P＜0.05). The performance of PCDHA4 ΔCt (when the cut-off was 6.34, the sensitivity was 64.6%, and the specificity was 91.5%) in the diagnosis of CIN grade 2 and above lesions was significantly better than of Thinprep cytologic test (TCT), HPV16/18, hrHPV and PCDHA4 (all P＜0.05). The performance of PCDHA4 ΔCt（when the cut-off was 5.45, the sensitivity was 74.2% and the specificity was 92.6%） in the diagnosis of CIN grade 3 and above lesions was also significantly better than that of TCT, HPV16/18, hrHPV and PCDHA4 (all P＜0.05). PCDHA4 ΔCt had better performance than TCT as a triage for non-16/18 hrHPV-positive women (all P＜0.05). Conclusions The detection of PCDHA4 gene methylation can serve as a potential biomarker for cervical cancer screening, which is helpful for the triage of hrHPV-positive population, and is of great significance for the early diagnosis of cervical cancer.