Limited Role of Promoter Methylation of MGMT and C13ORF18 in Triage of Low-Grade Squamous Intraepithelial Lesion

Sun, Lulu; Liu, Yuan; Sun, Xiaojiang; Pan, Leyun; Wu, Dan; Wang, Yudong

doi:10.4103/0366-6999.229896

Cited by 5 publications

(4 citation statements)

References 17 publications

(19 reference statements)

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“…The triage capacity of DNA methylation in our study was in accordance with previous reports [28,35]. However, studies on various DNA methylation triage methods in the Chinese population have reached conflicting conclusions [37][38][39]. These discrepancies reflect bias associated with the selected study populations and candidate genes.…”

Section: Discussionsupporting

confidence: 91%

DNA methylation for cervical cancer screening: a training set in China

Kong

Wang²,

Wang³

et al. 2020

Clin Epigenet

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Background: Despite rapid improvements in DNA methylation tools for cervical cancer screening, few robust, exploratory studies have been performed using the combination of two host genes, EPB41L3 and JAM3, newly developed assays. Methods: A review of abnormal liquid-based cytology and/or high-risk human papillomavirus (hrHPV) data from outpatient clinics in the study center from March 2018 to March 2019 was performed. Eligible patients with definitive histological pathology results were included, and their residual cytology samples were assessed for EPB41L3 and JAM3 methylation. The diagnostic accuracies of various screening strategies for definitive pathology and for cervical intraepithelial neoplasia (CIN) 2 or more severe lesions (CIN2+) were compared. Results: In total, 306 patients were successfully tested; 301 cases with cervical histological pathology were included in the final analysis, including 118 (39.2%) and 183 (60.8%) cases of inflammation/CIN1 and CIN2+, respectively. Regarding CIN2+ detection, methylation status and hrHPV plus methylation had similar positive predictive values (0.930 and 0.954, respectively, p = 0.395). Additionally, hrHPV, methylation, and hrHPV plus methylation had similar negative predictive values (0.612, 0.679, and 0.655, p = 0.677) that were significantly higher than that of cytology alone (0.250, p values 0.012, 0.001, and 0.001, respectively). For 49 cases with negative hrHPV results, positive methylation alone was able to differentiate CIN2+ from inflammation/CIN1. Conclusions: Methylation of both EPB41L3 and JAM3 is an accurate and feasible screening method for CIN2+.

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Section: Discussionsupporting

confidence: 91%

DNA methylation for cervical cancer screening: a training set in China

Kong

Wang²,

Wang³

et al. 2020

Clin Epigenet

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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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“…42,43 Promoter methylation of RUBCNL was identified as a potential biomarker for early diagnosis of cervical cancer. 44 BIRC3, baculoviral IAP repeat-containing protein 3, as an apoptosis inhibitor, was overexpressed in multiple cancers and led to development of malignant tumors. [45][46][47][48][49][50] Upregulation of BIRC3 promoted prostate cancer development and inhibited NK cell activities.…”

Section: Discussionmentioning

confidence: 99%

“…FADS3, as a fatty acid desaturase, was located along with FADS1 and FADS2, 41 which were reported to be associated with the occurrence and development of NSCLC and colon cancer 42,43 . Promoter methylation of RUBCNL was identified as a potential biomarker for early diagnosis of cervical cancer 44 . BIRC3, baculoviral IAP repeat‐containing protein 3, as an apoptosis inhibitor, was overexpressed in multiple cancers and led to development of malignant tumors 45–50 .…”

Section: Discussionmentioning

confidence: 99%