<scp>DNA</scp> methylation markers as triage test for the early identification of cervical lesions in a Chinese population

Li, Na; Hu, Y.; Zhang, Xinying; Liu, Yixin; He, Yongqing; Zee, Ate G.J. van der; Schuuring, Ed; Wisman, G. Bea A.

doi:10.1002/ijc.33430

Cited by 18 publications

(20 citation statements)

References 41 publications

(157 reference statements)

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“…In China, plenty of studies have been conducted in the recent years to explore the usage of methylation of human genes (including FAM19A4/EPB41L3/JAM3/MGMT/C13ORF18/ANKRD18CP/ C13ORF18/EPB41L3/JAM3/SOX1/ZSCAN1) in the field of cervical cancer screening, but all those studies were conducted in the clinic settings with relatively small sample size (ranging from 124 to 588). [19][20][21][22][23] Only one study indicated methylation test played a limited role, 21 the other studies showed that the methylation alone or in combination with HPV16/18 could be used as the primary screening testing or triage method for hrHPV positive women. The study with the largest sample size conducted by Gu et al supported that the S5 methylation panel at 2.85 cutoff was superior to HPV16/18 genotyping and cytology for histology HSIL+ (highgrade squamous intraepithelial lesion or worse) detection.…”

Section: Discussionmentioning

confidence: 99%

Triage performance and predictive value of the human gene methylation panel among women positive on self‐collected HPV test: Results from a prospective cohort study

Zhang

Zhao

et al. 2022

Intl Journal of Cancer

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Triaging of women positive for high‐risk human papillomavirus (hrHPV) on self‐collected samples requires a molecular reflex test to avoid recall for cytology or visual tests. We assessed triage performance and predictive value of human gene methylation panel (ZNF671/ASTN1/ITGA4/RXFP3/SOX17/DLX1) alone and with combination of HPV16/18 genotyping in a longitudinal screening study. Out of 9526 women at baseline, 1758 women positive for hrHPV on self‐collected samples followed up yearly were included in the current analysis. Satisfactory risk stratification to detect cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was demonstrated by the methylation panel with an odds ratio (OR) of 11.3 among methylation‐positive women compared to methylation‐negative counterparts. Triaging with methylation panel reduced colposcopy referral rate by 67.2% with sensitivity and specificity of 83.0% and 69.9% to detect CIN2+. The corresponding values for the combining methylation and HPV 16/18 were 96.6% and 58.3%. The cumulative 3‐year incident CIN2+ risk was 6.8% (95% CI: 4.9%‐8.6%) for hrHPV positive women, which was reduced to 4.5% (95% CI: 2.7%‐6.3%) and 2.9% (95% CI: 1.2%‐4.5%) for women negative on methylation triaging alone and negative on the combined strategy. The corresponding risk for women positive for both methylation and HPV 16/18 reached 33.7% (95% CI: 19.0%‐45.8%). Our study demonstrated the satisfactory triage performance and predictive value of the methylation panel, especially in combination with HPV 16/18 genotyping. The substantially lower risk of CIN2+ among the triage negative women over the next 3 years suggests that the interval for repeat HPV test can be safely extended to at least 2 years.

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Section: Discussionmentioning

confidence: 99%

Triage performance and predictive value of the human gene methylation panel among women positive on self‐collected HPV test: Results from a prospective cohort study

Zhang

Zhao

et al. 2022

Intl Journal of Cancer

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“…Then, the full text of the remaining 10 articles was carefully examined, and 4 uncontrolled studies were excluded due to the inability to extract data. Finally, the analysis included a total of six articles [13,[17][18][19][20][21].…”

Section: Process and Results Of Literature Searchmentioning

confidence: 99%

Exploring the Diagnostic Potential of EPB41L3 Methylation in Cervical Cancer and Precancerous Lesions: A Systematic Review and Meta-Analysis

Sha,

Liu,

Yang

et al. 2023

Gynecol Obstet Invest

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Objective: This meta-analysis aimed to comprehensively evaluate the diagnostic use of erythrocyte membrane protein band 4.1like3 (EPB41L3) methylation detection in cervical cancer (CC) and its precancerous lesions. Methods: CNKI, Wanfang, Cochrane Library, PubMed, and Ovid databases were searched using a combination of subject headings and free words. Pertinent data were retrieved after screening for inclusion and exclusion criteria, and the quality of the included studies was evaluated using QUADAS-2 criteria. The appropriate software was used for heterogeneity analysis and combined effect size calculation. Additionally, sensitivity analysis was used to evaluate the robustness of the combined results, and meta-regression and subgroup analysis were conducted to investigate the origins of heterogeneity. Results: This meta-analysis included six studies, including 525 healthy individuals, 182 cervical intraepithelial neoplasia 1 (CIN1) samples, 182 CIN2 samples, 281 CIN3 samples, and 226 CC samples. EPB41L3 methylation detection for CIN2 and above lesions demonstrated combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the curve of the comprehensive receiver operating characteristic curve of 0.67, 0.76, 3.19, 0.41, 7.60, and 0.80, respectively; CIN3 and above lesions demonstrated these evaluations at 0.73, 0.84, 4.35, 0.33, 23.94, and 0.90, respectively. Meta-regression analysis revealed that the population, time, sample type, detection method, literature quality, and sample size were not significant sources of heterogeneity affecting the combined diagnostic efficacy of CIN2 and above lesions (p > 0.05). Subgroup analysis revealed higher combined diagnostic values of CIN2 and above lesions in retrospective studies, tissue samples, and Chinese populations, with DORs of 41.03, 14.59, and 13.70, respectively. Conclusion: EPB41L3 methylation demonstrated a relatively low diagnostic performance in CC and precancerous lesions. However, it merits further investigation as a potential biomarker. Integrating it with multiple gene detection, human papillomavirus testing, and ThinPrep liquid-based cytology test examination is recommended to explore improved diagnostic strategies for CC and its precancerous lesions.

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“…JAM3, an adhesion and migration regulatory element, is considered a novel tumor suppressor gene for epigenetic reduction in colorectal cancers [26]. JAM3 is related to the 9 Disease Markers proliferation of cancer cells [27]. Knockdown of JAM3 inhibited the migration of renal cancer cells and promoted the apoptosis of renal cancer cells [28].…”

Section: Discussionmentioning

confidence: 99%

miR-127-5p Targets JAM3 to Regulate Ferroptosis, Proliferation, and Metastasis in Malignant Meningioma Cells

2022

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Objective. Meningiomas are one of the most common primary tumors of the central nervous system. Most of them are benign and can be cured by surgery, while a few meningiomas are malignant. Ferroptosis gene characteristics might be associated with drug therapy and survival in patients with clinically aggressive, unresectable meningiomas. This study explored the mechanism of differentially expressed miRNAs and ferroptosis in meningioma to provide a new reference to treat meningioma. Methods. Bioinformatics analysis of differential miRNA profiles and functions in patients with meningioma was performed. The contents of lactate dehydrogenase (LDH), malondialdehyde (MDA), and Fe2+ were determined. Reactive oxygen species (ROS) values, as well as cell cycle changes, were analyzed by flow cytometry. The targets of miR-127-5p and JAM3 were detected by dual luciferase assays. Cell counting kit-8 (CCK8) and Transwell assays were used to analyze cell activity. Ki67 expression was analyzed by immunohistochemistry. Expression levels of miR-127-5p and JAM3 were analyzed by RT-qPCR. GPX4 expression was quantified by western blotting. Results. miR-127-5p was expressed at low levels in IOMM-Lee cells, while JAM3 was highly expressed in IOMM-Lee cells. A dual luciferase assay demonstrated that miR-127-5p could target JAM3. Upregulation of miR-127-5p in IOMM-Lee cells resulted in cell cycle arrest and inhibition of cell activity. Upregulation of miR-127-5p increased LDH, MDA, and ROS levels and Fe2+ content and inhibited the expression of GPX4 protein. Upregulation of JAM3 reversed the results of miR-127-5p upregulation. Conclusion. miR-127-5p regulated meningioma formation and ferroptosis through JAM3, providing insights for the development of new treatments for meningioma.

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DNA methylation markers as triage test for the early identification of cervical lesions in a Chinese population

Cited by 18 publications

References 41 publications

Triage performance and predictive value of the human gene methylation panel among women positive on self‐collected HPV test: Results from a prospective cohort study

Triage performance and predictive value of the human gene methylation panel among women positive on self‐collected HPV test: Results from a prospective cohort study

Exploring the Diagnostic Potential of EPB41L3 Methylation in Cervical Cancer and Precancerous Lesions: A Systematic Review and Meta-Analysis

miR-127-5p Targets JAM3 to Regulate Ferroptosis, Proliferation, and Metastasis in Malignant Meningioma Cells

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