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.
Highlights
Endometrial cancer (EC) is the most frequently diagnosed malignancy of the female genital tract and the sixth most common cancer in women globally [1, 2]
While porphobilinogen and acetylcysteine discriminated between EC and the merged group of endometrial hyperplasia (EH) and healthy controls, there was no significant difference between EH and healthy controls [50]
A urine-based biomarker is ideal for EC detection and relies on the renal excretion of systemic biomarkers or urinary contamination with biomarkers shed from the uterus
Summary
Endometrial cancer (EC) is the most frequently diagnosed malignancy of the female genital tract and the sixth most common cancer in women globally [1, 2]. A similar study exploring unmet research needs in EC, found “which women with abnormal bleeding require urgent specialist referral and which can be safely reassured” to be second most important priority [30] Based on these gap analyses, studies exploring EC detection using non-invasive samples such as urine are urgently needed [28]. While renally excreted biomarkers may be difficult to measure due to the low abundance of tumorderived molecules in the circulation, especially in early stage EC, for uterine shed biomarkers, it is the consistency and reliability with which these contaminate urinary samples that limits their clinical utility, especially in asymptomatic women. Several techniques have potential for EC biomarker discovery and include cytology, spectroscopy, metabolomics, transcriptomics, and proteomics
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