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

Wang Juanjuan; Wu Wenting; Luo Ting; Rong Tingting

doi:10.3760/j.issn.1673-4777.2025.10.020

Abstract：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 △Ct 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 △Ct(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 △Ct(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 △Ct 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.