Expression of glucose-regulated protein 78 as prognostic biomarkers for triple-negative breast cancer

Histol Histopathol. 2020 Jun;35(6):559-568. doi: 10.14670/HH-18-185. Epub 2019 Nov 19.

Abstract

Introduction: Glucose-regulated protein78(GRP78) is a stress - induced endoplasmic reticulum chaperone protein. it is closely related to the occurrence, development, proliferation, differentiation and drug resistance of breast cancer. However, the association and clinicopathological features between GRP78 and triple negative breast cancer (TNBC) remain to be studied.

Material and methods: Clinical and pathological characteristics and overall survival were analysed retrospectively in 179 surgically resected TNBC patients. GRP78 was detected by immunohistochemistry (IHC) using breast cancer tissue microarrays (TMAs), and the association between GRP78 levels and clinicopathological factors and prognosis was analyzed. Furthermore, GRP78 expression in human TNBC and NTNBC cell lines was detected by Western blot and qRT-PCR. After Si-GRP78 knocked-down GRP78 in MDA-MB-231 and BT549 cell lines, cell proliferation was detected using Cell Counting Kit-8 (CCK-8) and cell colony formation was detected by crystal violet staining, respectively.

Results: GRP78 was expressed in triple negative breast cancer (TNBC). GRP78 expression was significantly associated with invasive, distant metastasis and proliferation of TNBC (P<0.05). In addition, patients with positive GRP78 expression had shorter overall survival (OS) and disease-free survival (DFS). And the high expression of GRP78 was significantly associated with disease-free survival (DFS) in patients with TNBC (P<0.001).

Conclusions: These findings improve our understanding of the expression pattern of GRP78 in TNBC and clarify the role of GRP78 as promising prognostic biomarkers for triple-negative breast cancer.

MeSH terms

  • Adult
  • Biomarkers, Tumor / metabolism
  • Disease-Free Survival
  • Endoplasmic Reticulum Chaperone BiP
  • Female
  • Glucose / metabolism
  • Heat-Shock Proteins* / isolation & purification
  • Heat-Shock Proteins* / metabolism
  • Humans
  • Middle Aged
  • Neoplasm Metastasis / pathology
  • Prognosis
  • Retrospective Studies
  • Triple Negative Breast Neoplasms / diagnosis*
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Heat-Shock Proteins
  • Glucose