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 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 p p p 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.

Document Details

Document Type
Pub Defense Publication
Publication Date
Feb 07, 2020
Source ID
10.1038/s41598-020-59116-x

Entities

People

  • Hisamori Kato
  • Louis Dubeau
  • Nouri Neamati
  • Paulette Mhawech-fauceglia
  • Rich Lieberman
  • Ronald J. Buckanovich
  • Shuzo Tamura
  • Soma Samanta
  • Yohei Miyagi
  • Yvonne G. Lin

Organizations

  • United States Army Medical Research and Development Command

Tags

Fields of Study

  • Biology

Readers

  • Breast cancer cell signaling and growth regulation.
  • Oncology (Cancer Research).
  • Oncology and Biomarker-Based Cancer Detection.