Combined Liquid Biopsy Methylation Analysis of CADM1 and MAL in Cervical Cancer Patients

Author:

Leffers Markus,Herbst JohannaORCID,Kropidlowski Jolanthe,Prieske Katharina,Bohnen Anna Lena,Peine Sven,Jaeger AnnaORCID,Oliveira-Ferrer Leticia,Goy Yvonne,Schmalfeldt Barbara,Pantel KlausORCID,Wölber Linn,Effenberger Katharina,Wikman HarrietORCID

Abstract

Cervical cancer is the fourth most common cancer in women, which is associated in >95% with a high-risk human papillomavirus (HPV) infection. Methylation of specific genes has been closely associated with the progress of cervical high-grade dysplastic lesions to invasive carcinomas. Therefore, DNA methylation has been proposed as a triage for women infected with high-risk HPV. Methylation analyses of cervical cancer tissue have shown that cell adhesion molecule 1 (CADM1) and myelin and lymphocyte protein (MAL) methylation are present in over 90% of all cervical high-grade neoplasias and invasive cervical cancers. Here, we established a liquid biopsy-based assay to detect MAL and CADM1 methylation in cell free (cf)DNA of cervical cancer. Methylation of the target gene was validated on bisulfite converted smear-DNA from cervical dysplasia patients and afterward applied to cfDNA using quantitative real-time PCR. In 52 smears, a combined analysis of CADM1 and/or MAL (CADM1/MAL) showed methylation in 86.5% of the cases. In cfDNA samples of 24 cervical cancer patients, CADM1/MAL methylation was detected in 83.3% of the cases. CADM1/MAL methylation was detected already in 81.8% of stage I-II patients showing the high sensitivity of this liquid biopsy assay. In combination with a specificity of 95.5% towards healthy donors (HD) and an area under the curve (AUC) of 0.872 in the receiver operating characteristic (ROC) analysis, CADM1/MAL cfDNA methylation detection might represent a novel and promising liquid biopsy marker in cervical cancer.

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Reference41 articles.

1. Global Cancer Observatory: Cancer Today https://gco.iarc.fr/today

2. The causal relation between human papillomavirus and cervical cancer

3. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors

4. HPV vaccination introduction worldwide and WHO and UNICEF estimates of national HPV immunization coverage 2010–2019

5. Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem;World Health Organization,2020

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