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The tumour-derived extracellular vesicle proteome varies by endometrial cancer histology and is confounded by an obesogenic environment
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  • Anastasiia Artuyants,
  • George Guo,
  • Marcella Flinterman,
  • Martin Middleditch,
  • Bincy Jacob,
  • Kate Lee,
  • Laura J. Vella,
  • Huaqi Su,
  • Michelle Wilson,
  • Lois Eva,
  • Andrew N. Shelling,
  • Cherie Blenkiron
Anastasiia Artuyants
The University of Auckland Faculty of Medical and Health Sciences
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George Guo
The University of Auckland
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Marcella Flinterman
The University of Auckland
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Martin Middleditch
The University of Auckland Faculty of Science
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Bincy Jacob
The University of Auckland Faculty of Science
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Kate Lee
The University of Auckland
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Laura J. Vella
The Florey Institute of Neuroscience and Mental Health
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Huaqi Su
The Florey Institute of Neuroscience and Mental Health
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Michelle Wilson
Auckland City Hospital
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Lois Eva
Auckland City Hospital
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Andrew N. Shelling
The University of Auckland
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Cherie Blenkiron
The University of Auckland

Corresponding Author:[email protected]

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Abstract

Endometrial cancer is the most prevalent gynaecological cancer globally. Its association with obesity and metabolic diseases is a key aetiology, increasingly among younger females. Early diagnosis and improved treatment decisions are crucial for these women whose outcomes could be improved by discovering new biomarkers. We took a new approach to extracellular vesicle (EV) biomarker discovery - profiling the proteome of enriched EVs isolated directly from frozen biobanked endometrial cancers. Nine tissue pools, each generating collagenase-digested tissue and matched small EVs, were analysed using label-free proteomics. Three clinical subgroups: Endometrioid low BMI (body mass index), Endometrioid high BMI, and Serous, irrespective of BMI, were compared to identify shared secreted proteins, proteins associated with histological subtype, and proteins related to BMI. EVs were enriched for common EV markers and large secreted proteins. Cell lysates were enriched in mitochondrial and blood proteins. EV protein profiles were most different between the high BMI subgroup and the others, highlighting a significant influence of comorbidities on the intra-tumoural EV secretome. Proteins differentially abundant between subgroups in tissues were strikingly not also differential in the matched EVs. This work has identified secreted proteins implicated in the complex pathophysiology of endometrial cancer and pinpointed candidate biomarkers for diagnosis.
14 Sep 2023Submitted to PROTEOMICS
15 Sep 2023Submission Checks Completed
15 Sep 2023Assigned to Editor
15 Sep 2023Review(s) Completed, Editorial Evaluation Pending
15 Sep 2023Reviewer(s) Assigned
15 Nov 2023Editorial Decision: Revise Minor
19 Feb 20241st Revision Received
20 Feb 2024Reviewer(s) Assigned
20 Mar 2024Review(s) Completed, Editorial Evaluation Pending
21 Mar 2024Editorial Decision: Revise Minor
04 Apr 2024Review(s) Completed, Editorial Evaluation Pending
04 Apr 20242nd Revision Received
05 Apr 2024Editorial Decision: Accept