Endometrial cancer represents the most prevalent gynaecological cancer globally. Its association with obesity and metabolic disorders is a cause for concern, particularly among younger females. Early diagnosis and improved treatment decisions are crucial for these individuals. Novel biomarker assays can significantly improve clinical management throughout their healthcare journey.
We applied an alternative approach to extracellular vesicle (EV) biomarker discovery by profiling the proteome of enriched EVs isolated from frozen biobanked endometrial cancers.
Our study involved nine pooled tissue preparations, each consisting of collagenase-digested tissue and small EVs isolated by size exclusion chromatography (F1). Samples were analysed using label-free proteomics. We focused on clinical subgroups: Endometrioid with low BMI, Endometrioid with high BMI, and Serous, irrespective of BMI. We aimed to identify shared secreted proteins, proteins associated with histological subtypes, and proteins related to obesity/BMI.
The F1 EVs were enriched for common EV markers, large secreted proteins, and/or proteins associated with exomeres or supermeres (VCP, MVP, CTLA). In contrast, cell lysates were enriched in mitochondrial proteins (IVD, HSD17B10) and circulating blood proteins (ALB, HBB). Comparison of tissues and EVs showed that the differential proteins were largely unique to the sample type with <3% overlap (ABHD11, ANXA5, ASRGL1, CNDP2, DDX27, EIF6, NOP2). Interestingly, EVs from the endometrioid subtype were enriched for MUC16 (cancer marker CA125). We observed an impact of obesity on EV protein cargos in the endometrioid subtype, with an expression of SLITs and ROBOs in low BMI samples.
The identified proteins can potentially serve as diagnostic biomarkers for endometrial cancer.