Abstract
ObjectiveProtein 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.MethodsTMA 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.ResultsWe 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).ConclusionsOur findings demonstrate that select PDI family members (PDI, PDIR, ERp72, ERp57 and AGR3) are potential prognostic markers for ovarian cancer.
Highlights
OVCAR-8, OVCAR-5, and OVCAR-3 cells (National Cancer Institute, Developmental Therapeutics Program, Bethesda, MD) were maintained in RPMI1640 supplemented with 10% heat-inactivated FBS (Gemini-Bioproducts)
Caov-3 were maintained in MEM supplemented with 10% heatinactivated FBS
Cells were grown as monolayers at 37oC in a humidified atmosphere of 5% CO2
Summary
OVCAR-8, OVCAR-5, and OVCAR-3 cells (National Cancer Institute, Developmental Therapeutics Program, Bethesda, MD) were maintained in RPMI1640 supplemented with 10% heat-inactivated FBS (Gemini-Bioproducts). NCI/ADR-RES cells (National Cancer Institute) were maintained in RPMI-1640 supplemented with 10% heat-inactivated FBS and 5 mmol/L L-glutamine.
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