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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2020-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-020-59116-x |
| _version_ | 1818427563698028544 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T14:47:43Z |
| format | Article |
| id | doaj.art-dd57821e5b494d9885f7af2c08ad84ce |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T14:47:43Z |
| publishDate | 2020-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-dd57821e5b494d9885f7af2c08ad84ce2022-12-21T22:57:14ZengNature PortfolioScientific Reports2045-23222020-02-0110111210.1038/s41598-020-59116-xClinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinomaSoma Samanta0Shuzo Tamura1Louis Dubeau2Paulette Mhawech-Fauceglia3Yohei Miyagi4Hisamori Kato5Rich Lieberman6Ronald J. Buckanovich7Yvonne G. Lin8Nouri Neamati9Department of Medicinal Chemistry, College of Pharmacy, Rogel Cancer Center, University of MichiganDepartment of Medicinal Chemistry, College of Pharmacy, Rogel Cancer Center, University of MichiganUSC/Norris Comprehensive Cancer Center and Department of Pathology, Keck School of Medicine of USC, 1441 Eastlake AvenueUSC/Norris Comprehensive Cancer Center and Department of Pathology, Keck School of Medicine of USC, 1441 Eastlake AvenueResearch Institute and Department of Gynecologic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-kuResearch Institute and Department of Gynecologic Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-kuDepartment of Internal Medicine, Division of Hematology-Oncology, Division of Gynecologic Oncology, University of MichiganDepartment of Internal Medicine, Division of Hematology-Oncology, Division of Gynecologic Oncology, University of MichiganUSC/Norris Comprehensive Cancer Center and Department of Obstetrics-Gynecology, Keck School of Medicine of USCDepartment of Medicinal Chemistry, College of Pharmacy, Rogel Cancer Center, University of MichiganAbstract 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.https://doi.org/10.1038/s41598-020-59116-x |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | Clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma |
| title_sort | clinicopathological significance of endoplasmic reticulum stress proteins in ovarian carcinoma |
| url | https://doi.org/10.1038/s41598-020-59116-x |
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