Non-invasive detection of endometrial cancer by DNA methylation analysis in urine

Abstract

Background The incidence of endometrial cancer is rising, and current diagnostics often require invasive biopsy procedures. Urine may offer an alternative sample type, which is easily accessible and allows repetitive self-sampling at home. Here, we set out to investigate the feasibility of endometrial cancer detection in urine using DNA methylation analysis. Results Urine samples of endometrial cancer patients (n = 42) and healthy controls (n = 46) were separated into three fractions (full void urine, urine sediment, and urine supernatant) and tested for three DNA methylation markers (GHSR, SST, ZIC1). Strong to very strong correlations (r = 0.77–0.92) were found amongst the different urine fractions. All DNA methylation markers showed increased methylation levels in patients as compared to controls, in all urine fractions. The highest diagnostic potential for endometrial cancer detection in urine was found in full void urine, with area under the receiver operating characteristic curve values ranging from 0.86 to 0.95. Conclusions This feasibility study demonstrates, for the first time, that DNA methylation analysis in urine could provide a non-invasive alternative for the detection of endometrial cancer. Further investigation is warranted to validate its clinical usefulness. Potential applications of this diagnostic approach include the screening of asymptomatic women, triaging women with postmenopausal bleeding symptoms, and monitoring women with increased endometrial cancer risk.

Hypermethylated CDO1 and ZNF454 in Cytological Specimens as Screening Biomarkers for Endometrial Cancer

“…Some studies proposed other minimally invasive and indirect methods to screen EC through the DNA methylation analysis, such as cervical scrapings, intravaginal tampons, and urine fractions ( 22 , 30 , 33 , 35 – 37 ). Huang et al.…”

“…DNA methylation analysis in urine provided an alternative for the detection of EC. In all urine fractions (full void, sediment, and supernatant), three DNA methylation markers ( GHSR , SST , and ZIC1 ) showed increased methylation levels in patients with EC as compared to controls, with AUC values ranging from 0.86 to 0.95 ( 37 ). The results seemed to be encouraging, but more exploration was needed.…”

Liquid Biopsies beyond Mutation Calling: Genomic and Epigenomic Features of Cell-Free DNA in Cancer

“…Moreover, successful methylation analysis of urinary cfDNA demonstrates the utility of urine for genomic [ 34 , 91 , 92 , 93 ], as well as epigenomic analysis. DNA methylation marks have been detected in urine sediment in various cancer types such as bladder cancer [ 94 ], endometrial cancer [ 95 ], and prostate cancer [ 96 ]. Additionally, urinary cfDNA equally offers the opportunity for DNA methylation analysis in colorectal cancer [ 97 ], bladder cancer [ 98 ], and RCC [ 34 ].…”

Diagnostic Accuracy of Liquid Biopsy in Endometrial Cancer

“…The procedure enables interrogation of tumor-derived material such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating free RNA (cfRNA), tumor-derived extracellular vesicles (EVs), and more recently, tumor educated platelets (TEPs), all present in the body fluids of cancer patients [ 1 , 2 ]. So far, mutational burden [ 3 ] and methylation pattern in ctDNA [ 4 ], along with circulating miRNA signatures [ 5 ], were used for screening and diagnosis of EC. Liquid biopsies as a diagnostic tool are expected to predict: (a) tumor aggressiveness with ctDNA level determination [ 6 ]; (b) relapse with ctDNA mutational profiling [ 7 ]; (c) recurrence risk using EV annexin A2 and L1CAM level analysis [ 8 ]; and (d) immunotherapy response by assessing microsatellite instability [ 9 ].…”