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

Abstract:

OBJECTIVE:The 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. METHODS:A 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. RESULTS:209 differentially expressed proteins were identified in a comparison of stage I endometrial 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). CONCLUSIONS:These 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.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Maxwell GL,Hood BL,Day R,Chandran U,Kirchner D,Kolli VS,Bateman NW,Allard J,Miller C,Sun M,Flint MS,Zahn C,Oliver J,Banerjee S,Litzi T,Parwani A,Sandburg G,Rose S,Becich MJ,Berchuck A,Kohn E,Risinger JI,Conrad

doi

10.1016/j.ygyno.2011.02.031

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

586-94

issue

3

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(11)00151-X

journal_volume

121

pub_type

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