Immunohistochemical Evidence for the Over-expression of Glutathione Peroxidase 3 in Clear Cell Type Ovarian Adenocarcinoma

Overview

Journal Med Oncol

Publisher Springer

Specialty Oncology

Date 2010 Aug 24

PMID 20730571

Citations 13

Authors

Hee Joong Lee

Jin Hwan Do

Sumi Bae

Sanghwa Yang

Xianglon Zhang

Ahwon Lee

Young Jin Choi

Dong Choon Park

Woong Shick Ahn

Affiliations

Soon will be listed here.

Abstract

Glutathione peroxidase 3 (GPX3) is a member of glutathione peroxidase family, exerting one of the most important cellular defense mechanisms against stress signals, including oxidative damage. In this study, the expression of GPX3 mRNA and protein was analyzed for ovarian cancer tissues to test its applicability as a biomarker that can distinguish the four major histologic types of epithelial ovarian cancer. A public microarray dataset containing 99 ovarian cancer and 4 normal ovary samples was downloaded, and GPX3 mRNA expression was analyzed. The expression of GPX3 protein was measured by immunohistochemical staining in 40 epithelial ovarian cancer tissues, 10 for each of the serous, endometrioid, mucinous, and clear cell type. Histoscores were made from the immunohistostaining, and analysis of variance (ANOVA) was performed to quantitate the differences in protein level. Analysis of genomic dataset confirms a GPX3 overexpression in clear cell type ovarian adenocarcinoma compared with normal ovary and 3 other subtypes of epithelial ovarian cancer at mRNA level. GPX3 also shows the highest average antibody staining intensities in clear cell type ovarian adenocarcinomas over the other 3 types in immunostaining on tissue arrays. This is the first validation of GPX3 as a clear cell type-specific biomarker in ovarian cancer patients' tissues by immunostaining. GPX3 may serve as an important molecular marker for the diagnosis and molecular understanding of clear cell carcinoma of the ovary.

Citing Articles

Brain gliomas new transcriptomic discoveries from differentially expressed genes to therapeutic targets.

Pei S, Jiang Z, Cheng H Sci Rep. 2025; 15(1):2553.

PMID: 39833228 PMC: 11746978. DOI: 10.1038/s41598-025-86316-0.

GPX3 supports ovarian cancer tumor progression in vivo and promotes expression of GDF15.

Chang C, Cheng Y, Kamlapurkar S, White S, Tang P, Elhaw A Gynecol Oncol. 2024; 185:8-16.

PMID: 38342006 PMC: 11179984. DOI: 10.1016/j.ygyno.2024.02.004.

Advances in the role of GPX3 in ovarian cancer (Review).

Geng D, Zhou Y, Wang M Int J Oncol. 2024; 64(3).

PMID: 38299269 PMC: 10836493. DOI: 10.3892/ijo.2024.5619.

Prognostic value and immunological roles of GPX3 in gastric cancer.

He Q, Chen N, Wang X, Li P, Liu L, Rong Z Int J Med Sci. 2023; 20(11):1399-1416.

PMID: 37790850 PMC: 10542182. DOI: 10.7150/ijms.85253.

Exploring the cellular and molecular differences between ovarian clear cell carcinoma and high-grade serous carcinoma using single-cell RNA sequencing and GEO gene expression signatures.

Guo D, Zhang S, Gao Y, Shi J, Wang X, Zhang Z Cell Biosci. 2023; 13(1):139.

PMID: 37525249 PMC: 10391916. DOI: 10.1186/s13578-023-01087-3.

References

C Mok S, Elias K, Wong K, Ho K, Bonome T, Birrer M . Biomarker discovery in epithelial ovarian cancer by genomic approaches. Adv Cancer Res. 2006; 96:1-22. DOI: 10.1016/S0065-230X(06)96001-1. View

Dobosy J, Roberts J, Fu V, Jarrard D . The expanding role of epigenetics in the development, diagnosis and treatment of prostate cancer and benign prostatic hyperplasia. J Urol. 2007; 177(3):822-31. DOI: 10.1016/j.juro.2006.10.063. View

Peng D, Razvi M, Chen H, Washington K, Roessner A, Schneider-Stock R . DNA hypermethylation regulates the expression of members of the Mu-class glutathione S-transferases and glutathione peroxidases in Barrett's adenocarcinoma. Gut. 2008; 58(1):5-15. PMC: 2845391. DOI: 10.1136/gut.2007.146290. View

Cannistra S . Cancer of the ovary. N Engl J Med. 2004; 351(24):2519-29. DOI: 10.1056/NEJMra041842. View

Schwartz D, Kardia S, Shedden K, Kuick R, Michailidis G, Taylor J . Gene expression in ovarian cancer reflects both morphology and biological behavior, distinguishing clear cell from other poor-prognosis ovarian carcinomas. Cancer Res. 2002; 62(16):4722-9. View

Yang S, Chung H . Novel biomarker candidates for gastric cancer. Oncol Rep. 2008; 19(3):675-80. View

Itamochi H, Kigawa J, Terakawa N . Mechanisms of chemoresistance and poor prognosis in ovarian clear cell carcinoma. Cancer Sci. 2008; 99(4):653-8. PMC: 11158134. DOI: 10.1111/j.1349-7006.2008.00747.x. View

Farley J, Ozbun L, Birrer M . Genomic analysis of epithelial ovarian cancer. Cell Res. 2008; 18(5):538-48. PMC: 7185304. DOI: 10.1038/cr.2008.52. View

Witton C, Hawe S, Cooke T, Bartlett J . Cyclooxygenase 2 (COX2) expression is associated with poor outcome in ER-negative, but not ER-positive, breast cancer. Histopathology. 2004; 45(1):47-54. DOI: 10.1111/j.1365-2559.2004.01898.x. View

10.

Lee O, Schneider-Stock R, McChesney P, Kuester D, Roessner A, Vieth M . Hypermethylation and loss of expression of glutathione peroxidase-3 in Barrett's tumorigenesis. Neoplasia. 2005; 7(9):854-61. PMC: 1501938. DOI: 10.1593/neo.05328. View

11.

Hough C, Cho K, Zonderman A, Schwartz D, Morin P . Coordinately up-regulated genes in ovarian cancer. Cancer Res. 2001; 61(10):3869-76. View

12.

Brigelius-Flohe R . Glutathione peroxidases and redox-regulated transcription factors. Biol Chem. 2006; 387(10-11):1329-35. DOI: 10.1515/BC.2006.166. View

13.

Comhair S, Erzurum S . The regulation and role of extracellular glutathione peroxidase. Antioxid Redox Signal. 2005; 7(1-2):72-9. DOI: 10.1089/ars.2005.7.72. View

14.

Sugiyama T, Kamura T, Kigawa J, Terakawa N, Kikuchi Y, Kita T . Clinical characteristics of clear cell carcinoma of the ovary: a distinct histologic type with poor prognosis and resistance to platinum-based chemotherapy. Cancer. 2000; 88(11):2584-9. View

15.

Olivier R, van Beurden M, van t Veer L . The role of gene expression profiling in the clinical management of ovarian cancer. Eur J Cancer. 2006; 42(17):2930-8. DOI: 10.1016/j.ejca.2006.04.013. View

16.

Yu Y, Yu G, Tseng G, Cieply K, Nelson J, DeFrances M . Glutathione peroxidase 3, deleted or methylated in prostate cancer, suppresses prostate cancer growth and metastasis. Cancer Res. 2007; 67(17):8043-50. DOI: 10.1158/0008-5472.CAN-07-0648. View

17.

Parkin D, Bray F, Ferlay J, Pisani P . Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2):74-108. DOI: 10.3322/canjclin.55.2.74. View

18.

Shimizu M, Nikaido T, Toki T, Shiozawa T, Fujii S . Clear cell carcinoma has an expression pattern of cell cycle regulatory molecules that is unique among ovarian adenocarcinomas. Cancer. 1999; 85(3):669-77. DOI: 10.1002/(sici)1097-0142(19990201)85:3<669::aid-cncr17>3.0.co;2-f. View

19.

Saga Y, Ohwada M, Suzuki M, Konno R, Kigawa J, Ueno S . Glutathione peroxidase 3 is a candidate mechanism of anticancer drug resistance of ovarian clear cell adenocarcinoma. Oncol Rep. 2008; 20(6):1299-303. View

20.

Beckett G, Arthur J . Selenium and endocrine systems. J Endocrinol. 2005; 184(3):455-65. DOI: 10.1677/joe.1.05971. View