GRP78 is Overexpressed in Non-small Cell Lung Cancer Tissues and is Associated with High VEGF Expression in Squamous Cell Carcinoma: A Pilot Study

Curr Cancer Drug Targets. 2023;23(10):805-816. doi: 10.2174/1568009623666230418111020.

Abstract

Background: Neovascularization is essential for the growth and progression of tumor tissues. GRP78 is frequently overexpressed in various cancers and has been suggested as a proangiogenic factor.

Purpose: This study aimed to investigate the expression levels of GRP78 and to test for significant relationships with the angiogenic markers, VEGF, and CD31.

Methods: In this study, paraffin-embedded NSCLC tissue samples (71 adenocarcinomas and 23 squamous cell carcinoma) were retrospectively collected from 94 patients with NSCLC. The expressions of VEGF, CD31, and GRP78 were determined by immunohistochemistry.

Results: High expression levels of VEGF and GRP78 were observed in 65 and 74 cases, respectively. Thirty-six patients expressed high CD31 levels. Adenocarcinomas expressed higher levels of the three proteins than squamous cell carcinomas (p-value < 0.05). Moreover, a statistically significant association was found between the expression levels of VEGF and CD31 (p-value = 0.001) and VEGF and GRP78 (p-value=0.028).

Conclusion: GRP78 overexpression was revealed in most of the investigated samples. The positive association between VEGF and GRP78 may indicate the proangiogenic role of GRP78 in lung cancer. Moreover, the positive association between VEGF and CD31 expression levels suggests that VEGF may cooperate with CD31 to promote angiogenesis in NSCLC.

Keywords: CD31; GRP78; NSCLC; VEGF; angiogenesis; cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma*
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Squamous Cell* / genetics
  • Endoplasmic Reticulum Chaperone BiP* / genetics
  • Humans
  • Lung Neoplasms* / genetics
  • Pilot Projects
  • Retrospective Studies
  • Vascular Endothelial Growth Factor A* / genetics

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • Vascular Endothelial Growth Factor A
  • HSPA5 protein, human
  • VEGFA protein, human