Proteomic analysis of stage I endometrial cancer tissue: Identification of proteins associated with oxidative processes and inflammation

ObjectiveThe present study aimed to identify differentially expressed proteins employing a high resolution mass spectrometry (MS)-based proteomic analysis of endometrial cancer cells harvested using laser microdissection.MethodsA differential MS-based proteomic analysis was conducted from discrete epithelial cell populations gathered by laser microdissection from 91 pathologically reviewed stage I endometrial cancer tissue samples (79 endometrioid and 12 serous) and 10 samples of normal endometrium from postmenopausal women. Hierarchical cluster analysis of protein abundance levels derived from a spectral count analysis revealed a number of proteins whose expression levels were common as well as unique to both histologic types. An independent set of endometrial cancer specimens from 394 patients were used to externally validate the differential expression of select proteins.Results209 differentially expressed proteins were identified in a comparison of stage I endoimetrial cancers and normal post-menopausal endometrium controls (Q < 0.005). A number of differentially abundant proteins in stage I endometrial cancer were identified and independently validated by western blot and tissue microarray analyses. Multiple proteins identified with elevated abundance in stage I endometrial cancer are functionally associated with inflammation (annexins) and oxidative processes (peroxiredoxins). PRDX1 and ANXA2 were both confirmed as being overexpressed in stage I cancer compared to normal endometrium by independent TMA (Q = 0.008 and Q = 0.00002 respectively).ConclusionsThese data provide the basis for further investigation of previously unrecognized novel pathways involved in early stage endometrial carcinogenesis and provide possible targets for prevention strategies that are inclusive of both endometrioid and serous histologic subtypes.

Research highlights
► Early endometrial carcinogenesis is associated with differentially expressed proteins associated with mitochondrial dysfunction.
► Peroxiredoxins are molecules that may promote cancer cell survival in stage I endometrial cancer.
► Annexins are anti-inflammatory molecules associated with early stage endometrial cancer.