The Role of VEGFA, COX2, HUR and CUGBP2 in Predicting the Response to Neoadjuvant Therapy in Rectal Cancer Patients

Medicina (Kaunas). 2020 Apr 22;56(4):192. doi: 10.3390/medicina56040192.

Abstract

Background and objectives: The effectiveness of neoadjuvant therapy, which is commonly used for stage II-III rectal cancer (RC) treatment, is limited. Genes associated with the pathogenesis of RC could determine response to this treatment. Therefore, the aim of this study was to investigate the potential predictive value of VEGFA, COX2, HUR and CUGBP2 genes and the associations between post-treatment changes in gene expression and the efficacy of neoadjuvant therapy. Materials and Methods: Biopsies from RC and healthy rectal tissue of 28 RC patients were collected before neoadjuvant therapy and 6-8 weeks after neoadjuvant therapy. The expression levels of VEGFA, COX2, HUR, CUGBP2 genes were evaluated using a quantitative real-time polymerase chain reaction. Results: The results reveal a significantly higher expression of VEGFA, COX2 and HUR mRNA in RC tissue compared to healthy rectal tissue (p < 0.05), and elevated VEGFA gene expression in pre-treatment tissues was associated with a better response to neoadjuvant therapy based on T-stage downstaging (p < 0.05). The expression of VEGFA, HUR and CUGBP2 genes significantly decreased after neoadjuvant therapy (p < 0.05). Responders to treatment demonstrated a significantly stronger decrease of VEGFA and COX2 expression after neoadjuvant therapy than non-responders (p < 0.05). Conclusions: The findings of this study suggest that the pre-treatment VEGFA gene expression might have predictive value for the response to neoadjuvant therapy, while the post-treatment decrease in VEGFA and COX2 gene expression could indicate the effectiveness of neoadjuvant therapy in RC patients.

Keywords: COX2; CUGBP2; HUR; VEGFA; neoadjuvant therapy; rectal cancer.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Biomarkers, Tumor
  • CELF Proteins / metabolism
  • Cyclooxygenase 2 / metabolism
  • ELAV-Like Protein 1 / metabolism
  • Female
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • Neoadjuvant Therapy / methods*
  • Neoplasm Staging
  • Nerve Tissue Proteins / metabolism
  • Rectal Neoplasms / genetics
  • Rectal Neoplasms / therapy*
  • Treatment Outcome
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Biomarkers, Tumor
  • CELF Proteins
  • CELF2 protein, human
  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • Nerve Tissue Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Cyclooxygenase 2