ABSTRACT
Objective:This work aims to explore the application value of cervical exfoliated cell DNA (Cysteine dioxygenase type 1, CDO1 and CUGBP Elav-like family member 4, CELF4) methylation in the detection of endometrial cancer in women of childbearing age. Methods:From November 2021 to October 2022, a prospective study was conducted on a total number of 517 reproductive-age women with abnormal uterine bleeding who had surgical indications for hysteroscopy at the Xiangya Third Hospital of Central South University. The cervical exfoliated cells were collected for cytology, HPV (human papillomavirus) and gene methylation detection before operation. Clinical information of patients, level of tumor-related biomarkers, and endometrial thickness of transvaginal ultrasound (TVS) were also collected. Single factor regression method was used to analyze the high-risk factors of endometrial cancer. Receiver operating characteristic curve analysis was used to obtain the area under the curve(AUC), focusing on the screening efficacy of gene methylation test for endometrial cancer in women of childbearing age.Results:The age, body mass index (BMI)≥25 kg/m 2, endometrial thickness≥11 mm, CDO1 m ΔCt≤8.4, CELF4 m ΔCt≤8.8, and double gene methylation were associated with endometrial cancer in women of childbearing age, 1.16(1.08-1.25), 4.33(1.89-10.31), 9.49(3.88-26.69), 69.62(25.70-224.36), 23.64(9.66-63.99), 87.39(24.83-555.05), all P<0.05. The AUC was 0.90 (95% CI 0.83-0.97) of CDO1 m/ CELF4 m in diagnosing endometrial carcinoma was higher than others factors, with sensitivity and specificity of 91.7% (95% CI 80.6%-100%) and 88.8% (95% CI 86.0%-91.6%). TVS combined with DNA methylation detection further improved the sensitivity to 95.8% (95% CI 87.8%-100%), but could not improve the specificity 68.0% (95% CI 63.8%-72.1%). Conclusions:For women of childbearing age with abnormal uterine bleeding or abnormal vaginal discharge, the accuracy of cervical cytology DNA methyl detection of endometrial cancer is better than other non-invasive clinical programs. DNA methylation combined with TVS can improve the sensitivity of detection.
ABSTRACT
Objective:Currently,traditional cervical cancer screening methods,such as high-risk human papillomavirus testing and liquid based cytology(LBC),still possess limitations.This study aims to identify new diagnostic biomarkers to achieve the goal of"precision screening"via exploring the clinical value of DNA methylation[ΔCtP:paired box gene 1(PAX1)and ΔCtJ:junctional adhesion molecule 3(JAM3)]detection in cervical exfoliated cells for the diagnosis of high-grade cervical lesions. Methods:A total of 136 patients who underwent gynecological examinations in the vaginal room of the Department of Gynecology at the Third Xiangya Hospital of Central South University from June 2021 to June 2022 were retrospectively studied.Among them,122 patients had non-high-grade cervical lesions,and 14 patients had high-grade cervical lesions.The variables included general information(age,body mass index,and menopause status),LBC,high-risk human papillomavirus,cervical tissue pathology,vaginal examination results,and the ΔCt values of JAM3 and PAX1 gene methylation.Logistic regression analysis was used to identify the factors affecting the diagnosis of high-grade cervical lesions,followed by correlation analysis and construction of a conditional inference tree model. Results:Logistic regression analysis showed that the methylation ΔCt values of PAX1 and JAM3 genes and LBC detection results were statistically significant between the high-grade cervical lesions group and the non-high-grade cervical lesions group(all P<0.05).Correlation analysis revealed a negative correlation between cervical pathological changes and ΔCtP(r=-0.36,P<0.001),ΔCtJ(r=-0.448,P<0.001),LBC(r=-0.305,P<0.001),or bacterial diversity(r=-0.183,P=0.037).The conditional inference tree showed that when ΔCtJ>10.13,all of patients had non-high-grade cervical lesions,while ΔCtP>6.22,the number of non-high-grade lesions accounted for 97.5%(117/120),and high-grade lesions accounted for only 2.5%(3/120).When ΔCtJ>8.61 and LBC were atypical squamous cell of undetermined significance or negative for intraepithelial lesions or malignancy(NILM),105(99.1%)patients were non-high-grade cervical lesions,only 1(0.9%)patient was high-grade lesion.When the results of LBC were high-grade lesions,only 9 patients'histopathological examination was the high-grade lesions and 3 non-high-grade lesions.When LBC indicated low-grade lesions,atypical squamous cell of undetermined significance,no intraepithelial lesions,and ΔCtP>6.22,117(97.5%)of patients'histopathological examination was the non-high-grade lesions. Conclusion:The JAM3/PAX1 gene methylation test can be used independently for the stratified diagnosis of high-grade/non-high-grade cervical lesions in women with high-risk human papillomavirus infection,independent of the cytological results of cervical excision.The JAM3/PAX1 gene methylation test can also be used in combination with LBC to make up for the shortcomings of low sensitivity of LBC.In addition,the application of methylation kit in large-scale cervical cancer screening in the future will be good to the detection of more patients with high-grade cervical lesions,and achieve early screening and early treatment for cervical lesions/cancer.
ABSTRACT
Objective:Uterine adhesion is mainly caused by endometrial injury,leading to poor postoperative pregnancy outcome.Therefore,preoperative evaluation on uterine cavity,especially endometrial condition,is very necessary.This study aims to explore the correlation between preoperative three-dimensional transvaginal ultrasound(3D-TVS)imaging characteristics and postoperative pregnancy outcomes after hysteroscopic adhesiolysis(HA). Methods:A total of 401 patients,who underwent HA surgery from February 22,2018 to October 31,2018 at the Third Xiangya Hospital of Central South University or Changsha Jiangwan Hospital,were enrolled,and we collected data regarding the preoperative 3D-TVS imaging characteristics and followed up their postoperative pregnancy outcomes.Correlation analysis and univariate and multivariate logistic regression analysis were performed between imaging features and pregnancy outcomes(live and non-live birth outcomes)in patients with intrauterine adhesion. Results:The results of correlation analysis showed that endometrial thickness,endometrial echo,visible tubal openings,endometrial blood flow,intercornual distance,and endometrial peristalsis were correlated with the live birth rate(all P<0.05).Logistic regression analysis revealed that in the HA patients with the live birth,the endometrial thickness was thicker(P<0.001),endometrial echo was more homogeneous(P<0.001),the number of tubal openings was more(P<0.001),the intercornual distance was wider(P<0.05),the endometrial blood flow,and irregular cases of endometrial peristaltic waves were more and cases of deficiency were fewer(both P<0.01)than those in the non-live birth group. Conclusion:Preoperative 3D-TVS imaging performance is closely related to pregnancy outcomes of HA patients,and preoperative 3D-TVS can be used to predict pregnancy outcomes after HA.