Study On The Clinical Value Of PAX1 And SOX1 Gene Methylation In Cervical Intraepithelial Lesions And Cervical Cancer

Objective: To quantitatively detect the methylation levels of PAX1 and SOX1 genes in exserted cervical cells by multiplex PCR fluorescence probe method.Combined with HPV,cytology,colposcopy and histopathological results,the methylation levels of PAX1 and SOX1 genes in different degrees of cervical lesions were investigated.To explore the relationship between different types of HPV infection and gene methylation level;The threshold values of PAX1 and SOX1 gene methylation in the detection and diagnosis of cervical cancer were calculated,and the diagnostic efficiency of them was analyzed.The advantages and disadvantages of TCT test,SOX1,PAX1 methylation test and HPV test were compared.Data and Methods: 30 patients with cervical cancer diagnosed in XX Hospital from June 2019 to February 2021 were collected as cervical cancer group,30 patients with high grade squamous intraepithelial lesion(HSIL)were selected as HSIL group,and 30 patients with low grade squamous intraepithelial lesion(LSIL)were selected as LSIL group.A total of 30 healthy women in the same period were collected as the healthy control group.HPV typing test results,cytological test results and colpophoscopic or histopathological examination results were collected from the four groups of patients(no such results were found in the healthy control group),and the methylation levels of SOX1 and PAX1 genes in exclinized cervical cells were quantitatively detected by specific multiplex PCR fluorescence probe method.Results:1.The methylation levels of PAX1 gene in exclaved cells of the control group,the LSIL group,the HSIL group and the cervical cancer group were 38.49±3.31,36.40±1.55,34.78±2.22,33.30±2.88,respectively,and the differences among groups were statistically significant(F=66.72,P<0.05).The methylation level of SOX1 gene was39.65±0.23,38.60±0.12,36.53±2.91 and 35.86±4.40,respectively,and the difference between groups was statistically significant(F=96.81,P<0.05).2.In patients infected with HPV16/18(high-risk carcinogenic type),the positive rates of SOX1 and PAX1 gene methylation were75.0%and89.6%;The positive rates of SOX1 and PAX1 methylation were 46.0% and 47.6% in patients infected with non-16/18 HPV.The positive rates of SOX1 and PAX1 methylation were 61.5% and73.1% in patients infected with HPV52/58.The positive rates of SOX1 and PAX1 methylation in patients with negative HPV test were 11.1% and 11.1%,with statistical differences among all groups(P<0.05).3.The methylation levels of PAX1 and SOX1 genes were detected,and the ROC curves were drawn to distinguish cervical cancer from non-cancer cancer,and the areas under the ROC curves were measured,which were 0.923(P<0.05)and 0.823(P<0.05),respectively.By calculation,when the cut-off value of PAX1 methylation level was29.03,the diagnostic efficiency was the best,and the sensitivity and specificity of PAX1 methylation level were 88.9% and 90% in the diagnosis of cervical cancer.By calculation,when the cut-off value of SOX1 methylation level was 30.56,the diagnostic efficiency was the best,and the sensitivity and specificity of the diagnosis of cervical cancer were 82% and 94%.4.The highest positive rate of PAX1 gene methylation detection was 100%;Among the positive cases using human papillomavirus(HPV)test,more than 50.84%of the cases were confirmed.Only less than 2.49% of the negative cases using thin-layer liquid-based cell test(TCT)were likely to develop cervical cancer;The specificity,sensitivity,negative predictive value and positive predictive value of PAX1 and SOX1 were 92.77%,87.10%,95.06% and 81.82%,respectively,when PAX1 and SOX1 genes were combined for detection.This combined detection method was better than that of two genes separately detected.Conclusion:1.There is PAX1 and SOX1 gene methylation phenomenon in cervical lesions and cervical cancer,and the gene methylation level is different in different levels of cervical lesions,and with the development of cervical lesions,the gene methylation level of both in cervical tissues is increased.2.The methylation levels of SOX1 and PAX1 genes in cervical exclaved cells were different with different HPV types infected by patients.The methylation levels of SOX1 and PAX1 genes in samples infected with HPV16/18 and HPV52/58 high-risk carcinogenic types were higher than those in patients infected with other HPV types and patients not infected with HPV.3.PAX1 and SOX1 gene methylation tests have high sensitivity and specificity in the diagnosis of cervical invasive cancer,and the best truncation values(29.03 and30.56)of PAX1 and SOX1 gene methylation tests according to ROC curve can be used in the differential diagnosis of cervical cancer.4.HPV and TCT had high positive predictive value and sensitivity,but low specificity;The methylation of PAX1 and SOX1 genes was detected with high specificity.The combined detection of PAX1 and SOX1 gene methylation was superior to the single detection.