title: Prognostic and Therapeutic Potential Implications of Genetic Variability in Prostaglandin E2 Pathway Genes in Rectal Cancer.
abstract: To evaluate the prognostic significance and potential therapeutic implication of genetic variability in prostaglandin E2pathway genes in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgery.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Digestive Surgery Service, Department of Surgery, Santo António Hospital, Hospital Center of Porto, Porto, Portugal marisadsantos@gmail.com.|Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.
authors.forename: Marisa D
authors.initials: MD
authors.lastname: Santos
authors.affiliation: Digestive Surgery Service, Department of Surgery, Santo António Hospital, Hospital Center of Porto, Porto, Portugal.|Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Silva
authors.affiliation: Digestive Surgery Service, Department of Surgery, Santo António Hospital, Hospital Center of Porto, Porto, Portugal.|Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.
authors.forename: Anabela
authors.initials: A
authors.lastname: Rocha
authors.affiliation: Digestive Surgery Service, Department of Surgery, Santo António Hospital, Hospital Center of Porto, Porto, Portugal.|Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Nogueira
authors.affiliation: Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.|Gastroenterology Service, Santo António Hospital, Hospital Center of Porto, Porto, Portugal.
authors.forename: Fernando
authors.initials: F
authors.lastname: Castro-Poças
authors.affiliation: Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.|Service of Medical Oncology, Santo António Hospital, Hospital Center of Porto, Porto, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Araujo
authors.affiliation: Department of Health Community, University of Porto, Porto, Portugal.
authors.forename: Eduarda
authors.initials: E
authors.lastname: Matos
authors.affiliation: Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.|Molecular Oncology and Viral Pathology Group, Investigation Centre, Portuguese Oncologic Institute, Porto, Portugal.|Research Department, Portuguese League Against Cancer, Porto, Portugal.
authors.forename: Carina
authors.initials: C
authors.lastname: Pereira
authors.affiliation: Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.|Molecular Oncology and Viral Pathology Group, Investigation Centre, Portuguese Oncologic Institute, Porto, Portugal.|Research Department, Portuguese League Against Cancer, Porto, Portugal.|CEBIMED, Faculty of Health Sciences of Fernando Pessoa, University of Porto, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
authors.affiliation: Abel Salazar Biomedical Science Institute, University of Porto, Porto, Portugal.|Pathological Anatomy Service, Department of Pathology, Santo António Hospital, Hospital Center of Porto, Porto, Portugal.|Department of Pathology and Molecular Immunology, University of Porto, Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D059248:Chemoradiotherapy; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery / Q000628:therapy; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015232:Dinoprostone; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C073492:ABCC4 protein, human
keywords: Mandard response; Molecular marker; neoadjuvant chemoradiation; polymorphism; prostaglandin E2 pathway genes; rectal cancer; survival