Expression of protein disulfide isomerase family members correlates with tumor progression and patient survival in ovarian cancer

蛋白质二硫键异构酶家族成员的表达与卵巢癌的肿瘤进展和患者生存相关

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作者:Soma Samanta, Shuzo Tamura, Louis Dubeau, Paulette Mhawech-Fauceglia, Yohei Miyagi, Hisamori Kato, Rich Lieberman, Ronald J Buckanovich, Yvonne G Lin, Nouri Neamati

Conclusions

Our findings demonstrate that select PDI family members (PDI, PDIR, ERp72, ERp57 and AGR3) are potential prognostic markers for ovarian cancer.

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.

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.

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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