Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma

Abstract Epithelial ovarian cancer (EOC) is a leading cause of cancer-related mortality in the United States due to the late-stage disease at diagnosis. Overexpression of GRP78 and PDI following endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) promote growth an...

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Autores principales:	Soma Samanta, Shuzo Tamura, Louis Dubeau, Paulette Mhawech-Fauceglia, Yohei Miyagi, Hisamori Kato, Rich Lieberman, Ronald J. Buckanovich, Yvonne G. Lin, Nouri Neamati
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dd57821e5b494d9885f7af2c08ad84ce
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spelling	oai:doaj.org-article:dd57821e5b494d9885f7af2c08ad84ce2021-12-02T14:06:58ZClinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma10.1038/s41598-020-59116-x2045-2322https://doaj.org/article/dd57821e5b494d9885f7af2c08ad84ce2020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-59116-xhttps://doaj.org/toc/2045-2322Abstract Epithelial ovarian cancer (EOC) is a leading cause of cancer-related mortality in the United States due to the late-stage disease at diagnosis. Overexpression of GRP78 and PDI following endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) promote growth and invasion in cancer. To identify novel prognostic biomarkers in EOC, here we determined the expression of ER stress-associated proteins (GRP78, ATF6 and PERK) and correlated with clinical outcome in EOC. Tissue microarray (TMA) samples from 415 tissues collected from three cancer centers (UM, USC, and KCCRI) were used to assess the expression levels of ER-associated proteins using immunohistochemistry (IHC). We observed that the expression levels of GRP78 (p < 0.0001), ATF6 (p < 0.0001), and PERK (p < 0.0001) were significantly increased in specimens of EOC compared to normal tissues, including in the serous subtype (p < 0.0001). Previously we reported that high expression of PDI correlated with poor patient survival in EOC. Here we showed that overexpression of GRP78 and PDI protein expression correlated with poor patient survival (p = 0.03), while low expression of combined GRP78 and PDI correlated with better survival (p = 0.01) in high-grade serous. The increased expression of ER stress-associated proteins in EOC suggests a role for ER stress and the UPR in EOC. More importantly, our results demonstrate that GRP78 and PDI are potential biomarkers for EOC and could be used as dual prognostic markers.Soma SamantaShuzo TamuraLouis DubeauPaulette Mhawech-FaucegliaYohei MiyagiHisamori KatoRich LiebermanRonald J. BuckanovichYvonne G. LinNouri NeamatiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Soma Samanta Shuzo Tamura Louis Dubeau Paulette Mhawech-Fauceglia Yohei Miyagi Hisamori Kato Rich Lieberman Ronald J. Buckanovich Yvonne G. Lin Nouri Neamati Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma
description	Abstract Epithelial ovarian cancer (EOC) is a leading cause of cancer-related mortality in the United States due to the late-stage disease at diagnosis. Overexpression of GRP78 and PDI following endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) promote growth and invasion in cancer. To identify novel prognostic biomarkers in EOC, here we determined the expression of ER stress-associated proteins (GRP78, ATF6 and PERK) and correlated with clinical outcome in EOC. Tissue microarray (TMA) samples from 415 tissues collected from three cancer centers (UM, USC, and KCCRI) were used to assess the expression levels of ER-associated proteins using immunohistochemistry (IHC). We observed that the expression levels of GRP78 (p < 0.0001), ATF6 (p < 0.0001), and PERK (p < 0.0001) were significantly increased in specimens of EOC compared to normal tissues, including in the serous subtype (p < 0.0001). Previously we reported that high expression of PDI correlated with poor patient survival in EOC. Here we showed that overexpression of GRP78 and PDI protein expression correlated with poor patient survival (p = 0.03), while low expression of combined GRP78 and PDI correlated with better survival (p = 0.01) in high-grade serous. The increased expression of ER stress-associated proteins in EOC suggests a role for ER stress and the UPR in EOC. More importantly, our results demonstrate that GRP78 and PDI are potential biomarkers for EOC and could be used as dual prognostic markers.
format	article
author	Soma Samanta Shuzo Tamura Louis Dubeau Paulette Mhawech-Fauceglia Yohei Miyagi Hisamori Kato Rich Lieberman Ronald J. Buckanovich Yvonne G. Lin Nouri Neamati
author_facet	Soma Samanta Shuzo Tamura Louis Dubeau Paulette Mhawech-Fauceglia Yohei Miyagi Hisamori Kato Rich Lieberman Ronald J. Buckanovich Yvonne G. Lin Nouri Neamati
author_sort	Soma Samanta
title	Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma
title_short	Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma
title_full	Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma
title_fullStr	Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma
title_full_unstemmed	Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma
title_sort	clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/dd57821e5b494d9885f7af2c08ad84ce
work_keys_str_mv	AT somasamanta clinicopathologicalsignificanceofendoplasmicreticulumstressproteinsinovariancarcinoma AT shuzotamura clinicopathologicalsignificanceofendoplasmicreticulumstressproteinsinovariancarcinoma AT louisdubeau clinicopathologicalsignificanceofendoplasmicreticulumstressproteinsinovariancarcinoma AT paulettemhawechfauceglia clinicopathologicalsignificanceofendoplasmicreticulumstressproteinsinovariancarcinoma AT yoheimiyagi clinicopathologicalsignificanceofendoplasmicreticulumstressproteinsinovariancarcinoma AT hisamorikato clinicopathologicalsignificanceofendoplasmicreticulumstressproteinsinovariancarcinoma AT richlieberman clinicopathologicalsignificanceofendoplasmicreticulumstressproteinsinovariancarcinoma AT ronaldjbuckanovich clinicopathologicalsignificanceofendoplasmicreticulumstressproteinsinovariancarcinoma AT yvonneglin clinicopathologicalsignificanceofendoplasmicreticulumstressproteinsinovariancarcinoma AT nourineamati clinicopathologicalsignificanceofendoplasmicreticulumstressproteinsinovariancarcinoma
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Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma

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