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.
Highlights
Ovarian cancer (OvCa) is not a single disease but is made up of several distinct subtypes, including serous, endometrioid, clear cell and mucinous
Deep proteomic analysis of tissue specimens To decipher the in-depth proteome of the tissues, we utilized an offline two-dimensional LC-mass spectrometry (MS)/MS workflow amenable to label-free quantification (LFQ) with minimal amount of protein required upfront (1mg total protein)
Correlation with clinical markers As an initial assessment of the accuracy of proteomic profiling, we investigated the expression of various immunohistochemical (IHC) markers used in histopathological analysis of endometriosis-associated ovarian cancers (Kalloger et al, 2011; Köbel et al, 2008; Köbel et al, 2014)
Summary
Ovarian cancer (OvCa) is not a single disease but is made up of several distinct subtypes, including serous, endometrioid, clear cell and mucinous. 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. 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. 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
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