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Article: Proteomic analysis of malignant and benign endometrium according to obesity and insulin-resistance status using Reverse Phase Protein Array

TitleProteomic analysis of malignant and benign endometrium according to obesity and insulin-resistance status using Reverse Phase Protein Array
Authors
Issue Date2020
Citation
Translational Research, 2020, v. 218, p. 57-72 How to Cite?
AbstractObesity and hyperinsulinemia are known risk factors for endometrial cancer, yet the biological pathways underlying this relationship are incompletely understood. This study investigated protein expression in endometrial cancer and benign tissue and its correlation with obesity and insulin resistance. One hundred and seven women undergoing hysterectomy for endometrial cancer or benign conditions provided a fasting blood sample and endometrial tissue. We performed proteomic expression according to body mass index, insulin resistance, and serum marker levels. We used linear regression and independent t test for statistical analysis. Proteomic data from 560 endometrial cancer cases from The Cancer Genome Atlas (TCGA) databank were used to assess reproducibility of results. One hundred and twenty seven proteins were significantly differentially expressed between 66 cancer and 26 benign patients. Protein expression involved in cell cycle progression, impacting cytoskeletal dynamics (PAK1) and cell survival (Rab 25), were most significantly altered. Obese women with cancer had increased PRAS40_pT246; a downstream marker of increased PI3K-AKT signaling. Obese women without cancer had increased mitogenic and antiapoptotic signaling by way of upregulation of Mcl-1, DUSP4, and Insulin Receptor-b. This exploratory study identified a number of candidate proteins specific to endometrioid endometrial cancer and benign endometrial tissues. Obesity and insulin resistance in women with benign endometrium leads to specific upregulation of proteins involved in insulin and driver oncogenic signaling pathways such as the PI3K-AKT-mTOR and growth factor signaling pathways which are mitogenic and also disruptive to metabolism.
Persistent Identifierhttp://hdl.handle.net/10722/341265
ISSN
2023 Impact Factor: 6.4
2023 SCImago Journal Rankings: 1.913
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorRaglan, Olivia-
dc.contributor.authorAssi, Nada-
dc.contributor.authorNautiyal, Jaya-
dc.contributor.authorLu, Haonan-
dc.contributor.authorGabra, Hani-
dc.contributor.authorGunter, Marc J.-
dc.contributor.authorKyrgiou, Maria-
dc.date.accessioned2024-03-13T08:41:27Z-
dc.date.available2024-03-13T08:41:27Z-
dc.date.issued2020-
dc.identifier.citationTranslational Research, 2020, v. 218, p. 57-72-
dc.identifier.issn1931-5244-
dc.identifier.urihttp://hdl.handle.net/10722/341265-
dc.description.abstractObesity and hyperinsulinemia are known risk factors for endometrial cancer, yet the biological pathways underlying this relationship are incompletely understood. This study investigated protein expression in endometrial cancer and benign tissue and its correlation with obesity and insulin resistance. One hundred and seven women undergoing hysterectomy for endometrial cancer or benign conditions provided a fasting blood sample and endometrial tissue. We performed proteomic expression according to body mass index, insulin resistance, and serum marker levels. We used linear regression and independent t test for statistical analysis. Proteomic data from 560 endometrial cancer cases from The Cancer Genome Atlas (TCGA) databank were used to assess reproducibility of results. One hundred and twenty seven proteins were significantly differentially expressed between 66 cancer and 26 benign patients. Protein expression involved in cell cycle progression, impacting cytoskeletal dynamics (PAK1) and cell survival (Rab 25), were most significantly altered. Obese women with cancer had increased PRAS40_pT246; a downstream marker of increased PI3K-AKT signaling. Obese women without cancer had increased mitogenic and antiapoptotic signaling by way of upregulation of Mcl-1, DUSP4, and Insulin Receptor-b. This exploratory study identified a number of candidate proteins specific to endometrioid endometrial cancer and benign endometrial tissues. Obesity and insulin resistance in women with benign endometrium leads to specific upregulation of proteins involved in insulin and driver oncogenic signaling pathways such as the PI3K-AKT-mTOR and growth factor signaling pathways which are mitogenic and also disruptive to metabolism.-
dc.languageeng-
dc.relation.ispartofTranslational Research-
dc.titleProteomic analysis of malignant and benign endometrium according to obesity and insulin-resistance status using Reverse Phase Protein Array-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.trsl.2019.12.003-
dc.identifier.pmid31954096-
dc.identifier.scopuseid_2-s2.0-85078031334-
dc.identifier.volume218-
dc.identifier.spage57-
dc.identifier.epage72-
dc.identifier.eissn1878-1810-
dc.identifier.isiWOS:000519662500005-

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