Association of cyclooxygenase-2 expression with endoplasmic reticulum stress and autophagy in triple-negative breast cancer

PLoS One. 2023 Aug 4;18(8):e0289627. doi: 10.1371/journal.pone.0289627. eCollection 2023.

Abstract

Cyclooxygenase-2 plays a role in oncogenesis and its overexpression is associated with triple-negative breast cancer. However, the mechanisms whereby cyclooxygenase-2 contribute to breast cancer are complex and not well understood. Cyclooxygenase-2 overexpression causes hypoxia, oxidative stress, and endoplasmic reticulum stress. The aim of this study is to investigate the correlations among cyclooxygenase-2 expression, endoplasmic reticulum stress-associated molecules, and autophagy-associated molecules in triple-negative breast cancer. Surgical specimens from two cohorts of triple-negative breast cancer patients without neoadjuvant systemic therapy were analyzed: cohorts 1 and 2 consisted of 218 cases from 2004 to 2006 and 221 cases from 2007 to 2009, respectively. Specimens were evaluated by immunohistochemical examination of cyclooxygenase-2, endoplasmic reticulum stress markers, and autophagy markers expression using tissue microarrays. Cyclooxygenase-2 was overexpressed in 29.8% and 23.9% of cases in cohorts 1 and 2, respectively; and it was positively correlated with two out of three endoplasmic reticulum stress-associated molecules (XBP1, p = 0.025 and p = 0.003 in cohort 1 and cohort 2, respectively; PERK, p < 0.001 in both cohorts). Cyclooxygenase-2 was also positively correlated with two out of three autophagy markers (p62, p = 0.002 and p = 0.003 in cohort 1 and cohort 2, respectively; beclin1, p < 0.001 in both cohorts). Although cyclooxygenase-2 was not an independent prognostic factor for distant metastasis free survival and overall survival, its expression was associated with the expression of endoplasmic reticulum stress and autophagy molecules in triple-negative breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Autophagy
  • Cyclooxygenase 2 / genetics
  • Endoplasmic Reticulum Stress
  • Humans
  • Oxidative Stress
  • Triple Negative Breast Neoplasms* / genetics

Substances

  • Cyclooxygenase 2
  • PTGS2 protein, human

Grants and funding

This work was supported by the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea (2019IP0732). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.