Abstract
Metabolic reprogramming is increasingly recognised as one of the defining hallmarks of tumorigenesis. There is compelling evidence to suggest that endometrial cancer develops and progresses in the context of profound metabolic dysfunction. Whilst the incidence of endometrial cancer continues to rise in parallel with the global epidemic of obesity, there are, as yet, no validated biomarkers that can aid risk prediction, early detection, prognostic evaluation or surveillance. Advances in high-throughput technologies have, in recent times, shown promise for biomarker discovery based on genomic, transcriptomic, proteomic and metabolomic platforms. Metabolomics, the large-scale study of metabolites, deals with the downstream products of the other omics technologies and thus best reflects the human phenotype. This review aims to provide a summary and critical synthesis of the existing literature with the ultimate goal of identifying the most promising metabolite biomarkers that can augment current endometrial cancer diagnostic, prognostic and recurrence surveillance strategies. Identified metabolites and their biochemical pathways are discussed in the context of what we know about endometrial carcinogenesis and their potential clinical utility is evaluated. Finally, we underscore the challenges inherent in metabolomic biomarker discovery and validation and provide fresh perspectives and directions for future endometrial cancer biomarker research.
Highlights
Endometrial cancer (EC) is the leading gynaecological malignancy in high-income countries and accounted for over 89,000 deaths worldwide in 2018 [1,2]
We have described the current status of EC metabolomic biomarker research and underscored the challenges inherent in biomarker discovery and validation
Amino acid and hormonal metabolites have all been reported as potential EC biomarkers for detection, prognosis and monitoring for disease recurrence
Summary
Endometrial cancer (EC) is the leading gynaecological malignancy in high-income countries and accounted for over 89,000 deaths worldwide in 2018 [1,2]. While the demographic shift towards an ageing population and declining rates of hysterectomy for benign gynaecological conditions contribute to these trends, the major cause is the growing prevalence of obesity (body mass index ≥ 30 kg/m2 ) [3,5]. Obesity has reached epidemic proportions, having nearly tripled in prevalence between 1975 and 2016 [6,7]. About 40% of the world female population aged 18 years and over are overweight and nearly 50% of endometrial cancers are directly attributable to obesity [6,8]
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