| Research Background:At present,the role of DNA methylation in the diagnosis of cervical cancer has received extensive attention,and more and more genes are considered as methylation biomarkers of cervical cancer.There are many studies about SOX1 gene methylation on cervical squamous cell carcinoma and its precancerous lesions.However,the diagnosis of cervical adenocarcinoma has always been a difficult problem in the early diagnosis of cervical cancer.Whether SOX1 gene methylation has similar diagnostic effect on cervical adenocarcinoma has not been confirmed by statistical analysis with large sample size.The overall diagnostic effect of SOX1 methylation on different types of cervical cancer,including cervical squamous cell carcinoma and cervical adenocarcinoma,still needs to be confirmed by a large number of clinical studies and systematic evaluation.Objective:To systematically evaluate the clinical accuracy of SOX1 gene methylation in the diagnosis of different types of cervical cancer by using meta-analysis,compare its diagnostic effect on cervical squamous cell carcinoma and cervical adenocarcinoma.The correlation between SOX1 gene methylation and different clinicopathological characteristics of cervical cancer was further analyzed by bioinformatics.To provide theoretical basis for the clinical diagnosis of different types of cervical cancer such as cervical squamous cell carcinoma and cervical adenocarcinoma by SOX1 methylation.Methods:Based on solving practical clinical problems to formulate appropriate retrieval strategies to retrieve relevant studies,we used computers to comprehensively search English databases such as Pub Med,Web of science,Embase,Cochrane Library,Clinical-Trail,and Chinese databases such as CNKI,VIP,CBM and Wanfang Database.The databases were searched from database creation to December 2022.Two researchers conducted strict independent screening,quality evaluation and data extraction according to inclusion criteria and exclusion criteria respectively.The data were extracted by combining Sensitivity,Specificity,PLR,NLR,DOR,SROC and other accuracy-related statistical indicators to assess the diagnostic.The paper also uses meta-regression analysis,subgroup analysis and sensitivity analysis to explore sources of heterogeneity.The meta-analysis was conducted using a combination of Review Manager 5.4,Stata 14.0 software and Meta-Disc 1.4.Bioinformatics analysis was performed by applying Disease Meth,UALCAN,DNMIVD and Meth Surv online databases,and the correlation of pathological features and prognostic value were explored by drawing methylation difference box diagram and survival curve.Results:1.A total of 19 studies from 13 publications with a total sample size of 3333 cases,including 1054 cases in the experimental group and 2279 cases in the control group,were included in this paper.The results showed that the combined Sen of SOX1 methylation in the diagnosis of cervical cancer was 0.87(95%CI: 0.85-0.89).Combined Spe was 0.80(95%CI: 0.78-0.82).PLR was 5.85(95%CI: 3.84-8.90);NLR was 0.16(95%CI: 0.13-0.19);DOR was 44.73(95%CI: 25.38-78.82);The AUC was0.9322.2.Analysis of four studies on cervical adenocarcinoma showed that the combined Sen of SOX1 methylation in diagnosis of cervical adenocarcinoma was 0.88(95%CI:0.84-0.92).Combined Spe was 0.88(95%CI: 0.81-0.92).PLR was 7.03(95%CI:1.54-32.00);NLR was 0.14(95%CI: 0.09-0.23);DOR was 73.91(95%CI:5.13-1064.41);The AUC was 0.9423.3.Analysis of 7 studies on cervical squamous cell carcinoma showed that the combined Sen of SOX1 methylation in diagnosis of cervical squamous cell carcinoma was 0.85(95%CI: 0.80-0.89).The combined Spe was 0.96(95%CI: 0.95-0.98).PLR was 18.88(95%CI: 5.48-65.08);NLR was 0.15(95%CI: 0.11-0.21).DOR was132.41(95%CI: 33.23-527.62);The AUC was 0.9182.4.In the subgroup analysis of SOX1 methylation in the diagnosis of different types of cervical cancer: sample size < 200 versus sample size ≥200 showed:(Sen=0.84)VS(Sen=0.91);(Spe=0.87)VS(Spe=0.75);(AUC=0.90)VS(AUC=0.97).Cervical tissue group versus cervical cell group showed:(Sen=0.87)VS(Sen=0.86);(Spe=0.64)VS(Spe=0.85);(AUC=0.91)VS(AUC= 0.94).Control group with precancerous lesion vs group without precancerous lesion showed:(Sen=0.86)VS(Sen=0.88);(Spe=0.74)VS(Spe=0.96);(AUC=0.91)VS(AUC= 0.94).5.Through bioinformatics analysis in different database platforms,the methylation level of SOX1 gene in cervical cancer samples was significantly higher than that in normal samples.In the inter-group analysis of different pathological types of cervical cancer,the methylation level of SOX1 gene was: Normal VS Adenosquamous(P=8.1670E-04);Normal VS Squamous(P=2.7616E-09);Normal VS Endocervical(P=2.0099E-11);Normal VS Mucinous(P=4.6768E-09);Normal VS Endometrioid(P=1.4954E-01);Squamous VS Endocervical(P=4.1035E-07);Endocervical VS Mucinous(P=2.7628E-03),and the methylation level was the highest in adenocarcinoma of the usual type.There was no significant difference in the methylation level of SOX1 gene among different age,race,tumor grade,tumor stage and tumor metastasis.6.Through bioinformatics analysis,it was found that the methylation level of cg11750165 locus in SOX1 gene had a significant impact on the overall survival of cervical cancer(P=0.0086<0.05),and high methylation level at this locus was associated with better prognosis of cervical cancer.Conclusions:1.SOX1 gene methylation has high diagnostic value for different types of cervical cancer,including cervical squamous cell carcinoma and cervical adenocarcinoma.2.Bioinformatics analysis showed that the methylation level of SOX1 gene was significantly higher in cervical squamous cell carcinoma,adenosquamous cell carcinoma and some HPV-associated adenocarcinomas than in normal samples,and the methylation level was the highest in adenocarcinoma of the usual type.In the meta-analysis,its sensitivity to the diagnosis of cervical adenocarcinoma was higher than that of squamous cell carcinoma,but its specificity was lower than that of squamous cell carcinoma.The application of SOX1 gene methylation is expected to improve the clinical detection rate of cervical adenocarcinoma.3.SOX1 gene methylation is more sensitive in the detection of large sample size,and can be used to screen cervical cancer in the population.4.In terms of sample types,the specificity of exuded cervical cells in the diagnosis of cervical cancer by SOX1 gene methylation is higher than that of cervical tissues,which provides ideas for shunting management in cervical screening.5.The diagnostic value of SOX1 methylation in distinguishing cervical cancer from normal subjects is higher than that in distinguishing cervical cancer from precancerous lesions.6.The degree of methylation of SOX1 gene is related to the prognosis of cervical cancer. |
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