34 Chapter 2 The majority of DNA methylation markers that hold promise for EC detection have been derived from studies on EC, but also markers developed for cervical cancer detection showed potential diagnostic relevance for EC detection (33). We considered the markers GHSR, SST and ZIC1 as interesting candidates to evaluate the detection of EC in the urine by DNA methylation marker testing, based on our previous studies on urinary methylation markers and their diagnostic marker potential for different cancer types (22, 23, 25, 34). This study investigates the feasibility of DNA methylation analysis in different urine fractions for the detection of EC. DNA methylation of genes GHSR, SST, and ZIC1 was analyzed in full void urine, urine sediment and urine supernatant samples of women with various types, histological grades and stages of EC and a healthy control group to determine the most optimal urine fraction and applicability of these genes for the detection of EC in the urine. METHODS Study population A total of 88 urine samples were used in this study, consecutively collected from women with EC (n = 42) and healthy female controls (n = 46). EC patients were recruited within the SOLUTION1 study which involved the collection of cervicovaginal and urine samples of women diagnosed with gynecological cancer. Samples from healthy female controls were collected through the Urine Controls (URIC) Biobank. Informed consent was acquired from each participating individual before urine collection. Ethical approval was obtained by the Medical Ethical Committee of the VU University Medical Center for both the SOLUTION1 study (no 2016.213) and the use of the URIC biobank (no 2017.112). Enrolled patients included women with histologically proven EC of any stage before receiving primary treatment. The revised American Joint Committee on Cancer/ Union for International Cancer Control Tumor-Node-Metastasis (TNM) Cancer Staging classification was used to determine tumor stage (35). Other patient characteristics that were documented included age, histological grade and EC type. Control urine samples were retrieved from the URIC biobank (n = 36), including healthy volunteers without any cancer diagnosis in the past 15 years, and from our previously published healthy control cohort (n = 10) (22).
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