Elevated Hu-Antigen Receptor (HuR) Expression is Associated with Tumor Aggressiveness and Poor Prognosis but not with COX-2 Expression in Invasive Breast Carcinoma Patients

Constantinos Giaginis, Anastasia Sampani, Ioly Kotta-Loizou, Ioanna Giannopoulou, Eugene Danas, Ekaterini Politi, Gerasimos Tsourouflis, Gregorios Kouraklis, Efstratios Patsouris, Antonios Keramopoulos, Lydia Nakopoulou, Stamatios Theocharis

Research output: Contribution to journalArticlepeer-review

Abstract

Hu-antigen R (HuR), a RNA-binding protein, is considered to play a crucial role in tumor development and progression by stabilizing or regulating a group of cellular mRNAs of cancer-related genes, such as cyclooxygenase-2 (COX-2). The present study aimed to evaluate the clinical significance of HuR and COX-2 expression in invasive breast carcinoma. HuR and COX-2 protein expression was assessed immunohistochemically on paraffin-embedded breast cancer tissue sections obtained from 121 patients and was statistically analyzed with clinicopathological parameters, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), as well as with tumor cells' proliferative capacity and overall and disease-free patients' survival. High HuR expression was positively associated with larger tumor size and advanced disease stage (p = 0.0234 and p = 0.0361, respectively), being more frequently observed in ER negative cases (p = 0.0208). High COX-2 expression was negatively associated with histological (p < 0.0001) and nuclear (p = 0.0033) grade and tumor cells' proliferative rate (p = 0.0015), being more frequently observed in luminal-A compared to other molecular subtypes (p = 0.0221). High HuR expression was associated with poor overall and disease-free patients' survival at both univariate (log-rank test, p = 0.0092 and p = 0.0004, respectively) and multivariate (Cox-regression analysis, p = 0.0223 and p = 0.0004, respectively) level. On the other hand, high COX-2 expression was associated with favorable overall and disease-free patients' survival merely at univariate level (log-rank test, p = 0.0389 and p = 0.0154, respectively). HuR expression was not associated with COX-2 expression (Spearman R = 0.1489, p = 0.1032). The present data support evidence that HuR is associated with tumor aggressiveness and poor prognosis in breast carcinoma, reinforcing its potential as promising therapeutic target in this type of neoplasia.

Original languageEnglish
Pages (from-to)631-640
Number of pages10
JournalPathology oncology research : POR
Volume24
Issue number3
DOIs
Publication statusPublished - Jul 2018

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor/metabolism
  • Breast Neoplasms/metabolism
  • Carcinoma, Ductal, Breast/metabolism
  • Carcinoma, Lobular/metabolism
  • Cyclooxygenase 2/metabolism
  • ELAV-Like Protein 1/metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Survival Rate

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