Application Of Gene Detection In Cervical Precancerous Lesions

Research background and purposeAs far as we know,Cervical cancer(CC)is the most common malignant tumor in gynecology,which is an important killer of women’s health.It can take 20 to 30 years or longer for patients with high-risk HPV(human papillmavirus)to progress from high-grade lesions to cervical cancer.This provides an opportunity to implement early screening for effective intervention.At present,the screening methods for cervical lesions in China are still high-risk HPV-DNA testing,Liquid-based cytology(TCT)and colposcopic biopsy when necessary.Due to the limited accuracy and sensitivity of traditional detection methods,it is necessary to explore effective molecular markers for early screening.The accurate typing and integration technology of HPV based on a new generation of high-throughput capture and sequencing platform is expected to be a molecular indicator for the detection of HPV integration status.In this paper,HPV-DNA gene integration and its clinical value in cervical precancerous lesions were deeply explored and studied by the above techniques.DNA methylation plays an indispensable role in the occurrence and development of tumors.In this paper,the application value of PAX1 methylation detection in the early diagnosis of cervical precancerous lesions was explored through the detection of samples of precancerous lesions at various stages.Research contents and methods1.A total of 927 patients who met the inclusion criteria were included in this study.The target gene region was captured through the preparation of whole genome DNA library,and then the HPV precise typing and integration technology of the new generation of high-throughput capture sequencing platform was used to explore the characteristics of HPV-DNA typing integration and the potential relationship between the degree of cervical precancerous lesions.2.In this study,a total of 130 eligible patients were recruited.By using PAX1 gene DNA methylation test combined with HPV-DNA typing test,the clinical correlation of PAX1 gene DNA methylation degree in the diagnosis and treatment of cervical precancerous lesions was explored.Research resultsPart Ⅰ:1.Among the 927 HPV typing and integration samples,83.28%were typed positive and 18.55%were integrated positive.Type 16 and type 18 accounted for the highest proportion of integrated positive in the samples.HPV-DNA integration is closely related to the development of cervical precancerous lesions,the HPV-DNA integration rate in the cervicitis group,CIN1 group,CIN2 group,CIN3 group was 32%,36%,40%,45%,with the increase of the degree of cervical lesions,HPV-DNA integration rate gradually increased.2.HPV-DNA tends to be relatively stable in the LCR region;HPV tends to integrate into intron and intergene regions.The Top three HF integrated genes were LRP1B,MACROD2 and FHIT.All of the above loci were found 10 times or more,and 12 genes were found in 6 samples(5.97%).Three genes were found in all the 10 samples(1.49%).3.Most of the hot integrated genes were related to the development of cancer.In particular,it affects the normal biological function of human genes and human cells in gene transcription and cell tight connection.Part Ⅱ:1.The lower the methylation value of PAX1,the more serious the lesion.The methylation value of PAX1 was related to the progression of cervical lesions and HPV infection type.2.The methylation value of PAX1 in single HPV16 positive and single HPV18 positive patients was significantly higher than that in non-HPV16/18 positive patients.3.In patients with Atypical squamous cells of undetermined Significance(ASCUS),the methylation of PAX1 in CIN2+was significantly higher than that in normal/CIN1.Conclusion1.HPV-DNA integration is closely related to the occurrence and development of cervical precancerous lesions,and the HPV-DNA integration rate gradually increases with the increase of the degree of cervical lesions.Cancer-related host gene dysfunction caused by integration may be the most important mechanism of HPV integration causing host cancer.2.PAX1 methylation detection is helpful for early identification of CIN3+and high-grade cervical lesions of ASCUS,and also helps to reduce the colposcopic referral rate of patients with ASCUS.