Urinary Biomarkers and Their Potential for the Non-Invasive Detection of Endometrial Cancer

Abstract

Endometrial cancer is the most common malignancy of the female genital tract and its incidence is rising in parallel with the mounting prevalence of obesity. Early diagnosis has great potential to improve outcomes as treatment can be curative, especially for early stage disease. Current tests and procedures for diagnosis are limited by insufficient accuracy in some and unacceptable levels of invasiveness and discomfort in others. There has, therefore, been a growing interest in the search for sensitive and specific biomarkers for endometrial cancer detection based on non-invasive sampling methodologies. Urine, the prototype non-invasive sample, is attractive for biomarker discovery as it is easily accessible and can be collected repeatedly and in quantity. Identification of urinary biomarkers for endometrial cancer detection relies on the excretion of systemic biomarkers by the kidneys or urinary contamination by biomarkers shed from the uterus. In this review, we present the current standing of the search for endometrial cancer urinary biomarkers based on cytology, genomic, transcriptomic, proteomic, and metabolomic platforms. We summarize the biomarker candidates and highlight the challenges inherent in urinary biomarker discovery. We review the various technologies with promise for biomarker detection and assess these novel approaches for endometrial cancer biomarker research.

Diagnostic accuracy of cytology for the detection of endometrial cancer in urine and vaginal samples

“…Urine had a sensitivity of 72.0%, which is inferior to vaginal cytology detection rates, but had the advantage of correctly identifying all but one of the tumours from other urogenital sites (specificity 94.9%), including a stage 3 ovarian cancer missed on vaginal cytology. Urine is a particularly attractive biofluid for endometrial cancer detection because it is straightforward to collect and highly acceptable to patients, offering opportunities for repeat sampling and collection at home 30 .…”

Detecting endometrial cancer

“…Initial studies have yielded promising results. 69 Blood biomarkers are also undergoing development. Cancer antigen 125 (CA125) is elevated in advanced stage, poor prognosis EC, but its relatively normal levels in early stage disease precludes its utility as an early detection tool.…”

“…It depends on urinary excretion of systemic cancer biomarkers, or the reliable contamination of urinary flow with uterine‐shed tumour debris. Initial studies have yielded promising results 69 . Blood biomarkers are also undergoing development.…”

Metabolomic Biomarkers for the Detection of Obesity-Driven Endometrial Cancer

“…Yet, no current screening programme exists for these high-risk women, partly because current diagnostics are invasive with low acceptability profiles and/or poor diagnostic accuracy [ 13 ]. A simple, minimally invasive endometrial cancer screening tool that can triage high-risk women for diagnostic workup, whilst safely reassuring those at low risk, would represent a major advance in the field [ 14 , 15 ].…”

“…High-throughput technologies and machine learning techniques have emerged as powerful tools for biomarker discovery and validation [ 15 , 16 , 17 , 18 , 19 ]. Metabolomics studies the downstream products of genomic, transcriptomic, and proteomic processes and best mirrors the human phenotype [ 20 , 21 ].…”