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

Maxwell, G. Larry; Hood, Brian L.; Day, Roger; Chandran, Uma; Kirchner, David; Kolli, V. S. Kumar; Bateman, Nicolas W.; Allard, Jay E.; Miller, Caela; Sun, Mai; Flint, Melanie S.; Zahn, Chris M.; Oliver, Julie; Banerjee, Subhadra; Litzi, Tracy; Parwani, Anil V.; Sandburg, Glenn; Rose, Scott; Becich, Michael J.; Berchuck, Andrew; Kohn, Elise C.; Risinger, John I.; Conrads, Thomas P.

doi:10.1016/j.ygyno.2011.02.031

Cited by 39 publications

(33 citation statements)

References 38 publications

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“…The full-length ANXA2 is an estrogenresponsive protein involved in cell motility and proliferation in normal and transformed cells, known to be up-regulated in EEC and ESC. Contrary to the previous results, 21 in our experimental settings, ANXA2 appears not modified in neoplastic EEC tissues, whereas the shorter H0YN42 form is consistently up-regulated in the same samples. Indeed, 2DE gel analysis (ie, isoelectric point and molecular mass) strongly supports the evidence that the protein spot, whose expression varies among neoplastic and healthy tissue, is related to the H0YN42, not the ANXA2 full-length protein (Fig.…”

Section: Discussioncontrasting

confidence: 99%

DJ-1 in Endometrial Cancer: A Possible Biomarker to Improve Differential Diagnosis Between Subtypes

Morelli¹,

Scumaci²,

Cello³

et al. 2014

Int J Gynecol Cancer

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Section: Discussioncontrasting

confidence: 99%

DJ-1 in Endometrial Cancer: A Possible Biomarker to Improve Differential Diagnosis Between Subtypes

Morelli¹,

Scumaci²,

Cello³

et al. 2014

Int J Gynecol Cancer

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“…Among the STAT1-associated genes, ICAM-1, PD-L1, and SMAD7 are involved in cancer immunity (43), and proteomic analysis revealed multiple proteins associated with inflammation are overexpressed in the uterus with endometrial cancer (44). Immunohistochemical staining demonstrated that SPEC has a characteristic tumor microenvironment at its invasive front that is fully infiltrated by CD8 þ immune cells ( Fig.…”

Section: Discussionmentioning

confidence: 99%

STAT1 Drives Tumor Progression in Serous Papillary Endometrial Cancer

et al. 2014

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Recent studies of the interferon-induced transcription factor STAT1 have associated its dysregulation with poor prognosis in some cancers, but its mechanistic contributions are not well defined. In this study, we report that the STAT1 pathway is constitutively upregulated in type II endometrial cancers. STAT1 pathway alteration was especially prominent in serous papillary endometrial cancers (SPEC) that are refractive to therapy. Our results defined a "SPEC signature" as a molecular definition of its malignant features and poor prognosis. Specifically, we found that STAT1 regulated MYC as well as ICAM1, PD-L1, and SMAD7, as well as the capacity for proliferation, adhesion, migration, invasion, and in vivo tumorigenecity in cells with a high SPEC signature. Together, our results define STAT1 as a driver oncogene in SPEC that modulates disease progression. We propose that STAT1 functions as a prosurvival gene in SPEC, in a manner important to tumor progression, and that STAT1 may be a novel target for molecular therapy in this disease. Cancer Res; 74(22); 6519-30. Ó2014 AACR.

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“…Recently the use of proteomics in reproductive biology has increased, and its use in developing biomarkers is thought to be critical if we are to progress in understanding the basis of disease and fertility defects [11][12][13][14][15][16][17][18][19][20]. Despite the opportunity for proteomics to add to our molecular understanding of organ-specific tissues, the cycling premenopausal human endometrium has not enjoyed such attention to date [21].…”

Section: Introductionmentioning

confidence: 99%

Proteomics of the Human Endometrial Glandular Epithelium and Stroma from the Proliferative and Secretory Phases of the Menstrual Cycle1

Hood

Liu

Alkhas

et al. 2015

Biology of Reproduction

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Despite its importance in reproductive biology and women's health, a detailed molecular-level understanding of the human endometrium is lacking. Indeed, no comprehensive studies have been undertaken to elucidate the important protein expression differences between the endometrial glandular epithelium and surrounding stroma during the proliferative and midsecretory phases of the menstrual cycle. We utilized laser microdissection to harvest epithelial cells and stromal compartments from proliferative and secretory premenopausal endometrial tissue and performed a global, quantitative mass spectrometry-based proteomics analysis. This analysis identified 1224 total proteins from epithelial cells, among which 318 were differentially abundant between the proliferative and secretory phases (q < 0.05), and 1005 proteins from the stromal compartments, 19 of which were differentially abundant between the phases (q < 0.05). Several proteins were chosen for validation by immunohistochemistry in an independent set of uterine tissues, including carboxypeptidase M, tenascin C, neprilysin, and ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP3). ENPP3, which was elevated in epithelial glandular cells in the secretory phase, was confirmed to be elevated in midsecretory-phase baboon uterine lavage samples and also observed to have an N-linked glycosylated form that was not observed in the proliferative phase. This study provides a detailed view into the global proteomic alterations of the epithelial cells and stromal compartments of the cycling premenopausal endometrium. These proteomic alterations during endometrial remodeling provide a basis for numerous follow-up investigations on the function of these differentially regulated proteins and their role in reproductive biology and endometrial pathologies.

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

Abstract: 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.

Cited by 39 publications

References 38 publications

DJ-1 in Endometrial Cancer: A Possible Biomarker to Improve Differential Diagnosis Between Subtypes

DJ-1 in Endometrial Cancer: A Possible Biomarker to Improve Differential Diagnosis Between Subtypes

STAT1 Drives Tumor Progression in Serous Papillary Endometrial Cancer

Proteomics of the Human Endometrial Glandular Epithelium and Stroma from the Proliferative and Secretory Phases of the Menstrual Cycle1

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