title: Specific gene expression profiles are associated with a pathologic complete response to neoadjuvant therapy in esophageal adenocarcinoma.
abstract: BACKGROUND
  Predicting treatment response to chemo-radiotherapy (CRT) in esophageal cancer remains an unrealized goal despite studies linking constellations of genes to prognosis. We aimed to determine if specific expression profiles are associated with pathologic complete response (pCR) after neoadjuvant CRT.
  
  
  METHODS
  Eleven genes previously associated with esophageal cancer prognosis were identified. Esophageal adenocarcinoma (EAC) patients treated with neoadjuvant CRT and esophagectomy were included. Patients were classified into two groups: pCR and no-or-incomplete response (NR). Polymerase chain reaction was used to evaluate gene expression. Omnibus testing was applied to overall gene expression differences between groups, and log-rank tests compared individual genes.
  
  
  RESULTS
  Eleven pCR and eighteen NR patients were analyzed. Combined expression profiles were significantly different between pCR and NR groups (p < 0.01). The gene CCL28 was over-expressed in pCR patients (Log-HR: 1.53, 95%CI: 0.46-2.59, p = 0.005), and DKK3 was under-expressed in pCR (Log-HR: -1.03 95%CI: -1.97, -0.10, p = 0.031).
  
  
  CONCLUSIONS
  EAC tumors that demonstrated a pCR have genetic profiles that are significantly different from typical NR profiles. The genes CCL28 and DKK3 are potential predictors of treatment response.
authors.affiliation: Department of Surgery, Division of Gastrointestinal and General Surgery, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McLaren
authors.affiliation: Knight Cardiovascular Institute, Department of Medicine, Oregon Health & Science University, Portland, OR, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Barnes
authors.affiliation: Department of Surgery, Division of Gastrointestinal and General Surgery, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Willy Z
authors.initials: WZ
authors.lastname: Terrell
authors.affiliation: Department of Medicine, Division of Medical Oncology, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Vaccaro
authors.affiliation: School of Public Health, Division of Biostatistics, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Wiedrick
authors.affiliation: Department of Surgery, Division of Gastrointestinal and General Surgery, Oregon Health and Science University, Portland, OR, USA.
authors.forename: John G
authors.initials: JG
authors.lastname: Hunter
authors.affiliation: Department of Surgery, Division of Gastrointestinal and General Surgery, Oregon Health and Science University, Portland, OR, USA. Electronic address: dolanj@ohsu.edu.
authors.forename: James P
authors.initials: JP
authors.lastname: Dolan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D059186:Chemoradiotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012042:Registries; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarker; Esophageal cancer; Gene expression; Neoadjuvant therapy; Pathologic complete response