Prognostic and Therapeutic Potential Implications of Genetic Variability in Prostaglandin E2 Pathway Genes in Rectal Cancer

Anticancer Res. 2017 Jan;37(1):281-291. doi: 10.21873/anticanres.11319.

Abstract

Aim: To evaluate the prognostic significance and potential therapeutic implication of genetic variability in prostaglandin E2 pathway genes in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgery.

Materials and methods: This cohort study included 167 patients with LARC, treated with nCRT followed by surgery. A total of 61 single nucleotide polymorphisms (SNPs) were characterized using the Sequenom platform through multiplex amplification followed by mass-spectometric product separation. Surgical specimens were classified according to Mandard tumor regression grade (TRG). The patients were divided as 'good responders' (Mandard TGR1-2) and 'poor responders' (Mandard TRG3-5). We examined prognostic value of polymorphisms studied to determine if they are related to Mandard response.

Results: Mandard tumor response and rs17268122 in ATP binding cassette subfamily C member (ABCC4) gene were the only two parameters with independent prognostic significance for disease-free survival.

Conclusion: tagSNP ABCC4 rs17268122 appears to be a prognostic factor in LARC treated with nCRT and surgery, independently of response to nCRT. The screening of ABCC4 rs17268122 tagSNP and the Mandard tumor response in clinical practice may help to identify patients with different rectal cancer prognosis and contribute to an individualized therapeutic decision tree.

Keywords: Mandard response; Molecular marker; neoadjuvant chemoradiation; polymorphism; prostaglandin E2 pathway genes; rectal cancer; survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Chemoradiotherapy
  • Dinoprostone / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics*
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide
  • Prognosis
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / surgery
  • Rectal Neoplasms / therapy
  • Signal Transduction
  • Treatment Outcome

Substances

  • ABCC4 protein, human
  • Antineoplastic Agents
  • Multidrug Resistance-Associated Proteins
  • Dinoprostone