Unraveling endometriosis-associated ovarian carcinomas using integrative proteomics

Abstract

Background: To elucidate potential markers of endometriosis and endometriosis-associated endometrioid and clear cell ovarian carcinomas using mass spectrometry-based proteomics. Methods: A total of 21 fresh, frozen tissues from patients diagnosed with clear cell carcinoma, endometrioid carcinoma, endometriosis and benign endometrium were subjected to an in-depth liquid chromatography-tandem mass spectrometry analysis on the Q-Exactive Plus. Protein identification and quantification were performed using MaxQuant, while downstream analyses were performed using Perseus and various bioinformatics databases. Results: Approximately 9000 proteins were identified in total, representing the first in-depth proteomic investigation of endometriosis and its associated cancers. This proteomic data was shown to be biologically sound, with minimal variation within patient cohorts and recapitulation of known markers. While moderate concordance with genomic data was observed, it was shown that such data are limited in their abilities to represent tumours on the protein level and to distinguish tumours from their benign precursors. Conclusions: The proteomic data suggests that distinct markers may differentiate endometrioid and clear cell carcinoma from endometriosis. These markers may be indicators of pathobiology but will need to be further investigated. Ultimately, this dataset may serve as a basis to unravel the underlying biology of the endometrioid and clear cell cancers with respect to their endometriotic origins.

A Review of the Clinical Characteristics and Novel Molecular Subtypes of Endometrioid Ovarian Cancer

“…In proteomics, distinct markers may distinguish EOVC from other histological types. Serous tumor markers such as WT1, P53, CK20, and mucinous tumor markers such as CEA and MUC2 are not often expressed in EOVC and OCCC, and EOVC–specific markers such as ER, PR, TFF3, DKK1, and MMP7 display near-exclusive expression in EOVC ( 90 ). Current studies have found that the status of WT1, P53, Napsin-A are helpful in reducing the rate of misdiagnosis of EOVC ( 88 , 89 , 91 , 92 ).…”

Unraveling endometriosis-associated ovarian carcinomas using integrative proteomics

“…The spreadsheet contains the details of the identification and quantitation of all proteins across the 21 biological samples. 10.5256/f1000research.13863.d193821 ( Leung et al , 2018b)…”