Expression of protein disulfide isomerase family members correlates with tumor progression and patient survival in ovarian cancer
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Soma Samanta1, Shuzo Tamura1, Louis Dubeau2, Paulette Mhawech-Fauceglia2, Yohei Miyagi3, Hisamori Kato3, Rich Lieberman4, Ronald J. Buckanovich4,5, Yvonne G. Lin2,6 and Nouri Neamati1
1Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan
2USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
3Kanagawa Cancer Center Research Institute, Yokohama, Japan
4Department of Internal Medicine, Division of Hematology Oncology, Division of Gynecologic Oncology, University of Michigan, Ann Arbor, Michigan
5Current/Present affiliation: Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA
6Current/Present affiliation: Genentech-Roche, South San Francisco, California, USA
Nouri Neamati, email: firstname.lastname@example.org
Keywords: tissue microarray (TMA), ovarian cancer, PDI family proteins, clinical outcome, patient survival
Received: June 04, 2017 Accepted: September 07, 2017 Published: October 06, 2017
Objective: Protein disulfide isomerase (PDI) is an oxidoreductase that is overexpressed in several cancers. PDI family members (PDIs) play a role in various diseases including cancer. Select PDIs were reported as useful markers in other cancers but their expression in ovarian cancer has not been thoroughly assessed. We sought to evaluate the expression of PDI, PDIA6, PDIR, ERp57, ERp72 and AGR3 in ovarian cancer patient samples and examine their prognostic significance.
Methods: TMA samples from 415 tissues collected from three cancer centers (UM, USC, and KCCRI) were used to assess the expression levels of PDI family proteins using IHC.
Results: We observed significant increases in PDI (p = 9.16E-36), PDIA6 (p = 5.51E-33), PDIR (p = 1.81E-12), ERp57 (p = 9.13E-07), ERp72 (p = 3.65E-22), and AGR3 (p = 4.56E-24) expression in ovarian cancers compared to normal tissues. Expression of PDI family members also increases during disease progression (p <0.001). All PDI family members are overexpressed in serous ovarian cancer (p<0.001). However, PDI, PDIA6, PDIR, ERp72 and AGR3 are more significantly overexpressed (p<0.001) than ERp57 (p<0.05) in clear cell ovarian carcinoma. Importantly, overexpression of PDI family members is associated with poor survival in ovarian cancer (p = 0.045 for PDI, p = 0.047 for PDIR, p = 0.037 for ERp57, p = 0.046 for ERp72, p = 0.040 for AGR3) with the exception of PDIA6 (p = 0.381).
Conclusions: Our findings demonstrate that select PDI family members (PDI, PDIR, ERp72, ERp57 and AGR3) are potential prognostic markers for ovarian cancer.
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