title: A validated miRNA profile predicts response to therapy in esophageal adenocarcinoma.
abstract: BACKGROUND
  In the current study we present a validated miRNA signature to predict pathologic complete response (pCR) to neoadjuvant chemoradiation in esophageal adenocarcinoma.
  
  
  METHODS
  Three patient cohorts (discovery, n = 10; model, n = 43; and validation, n = 65) with locally advanced esophageal adenocarcinoma were analyzed. In the discovery cohort 754 miRNAs were examined in pretreatment tumor biopsy specimens using a TaqMan array. Of these, the 44 most significantly altered between tumors with pCR and non-pCR were examined in an additional 43 tumors using a Fluidigm 48.48 array. The 4 miRNAs (mir-505*, mir-99b, mir-451, and mir-145*) significantly predicting pCR in both cohorts were examined in an additional validation cohort (n = 65) using an Illumina array. These 4 miRNAs were used to generate an miRNA expression profile (MEP) score.
  
  
  RESULTS
  The 4 miRNAs profiled are highly significantly associated with pCR in the model cohort (Ptrend  = .008), the validation cohort (Ptrend  = .025), and the combined cohort (Ptrend  = 4.6 × 10(-4) ). The receiver-operator characteristic areas under the curves (AUCs) for the MEP score were 0.78 for the model cohort, 0.71 for the validation cohort, and 0.72 for the combined cohort. When combined with clinical variables, the MEP score AUCs increased to 0.89, 0.77, and 0.81, respectively Estimates from logistic regression based on the MEP were determined and used to generate a probability of pCR plot, which identifies a group of patients with very high (≥80%) and very low (≤10%) probability of pCR.
  
  
  CONCLUSIONS
  The MEP score provides a validated means of predicting pCR to neoadjuvant chemoradiotherapy in esophageal adenocarcinoma that is robust across several analysis platforms.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Heath D
authors.initials: HD
authors.lastname: Skinner
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Lee
authors.forename: Manoop S
authors.initials: MS
authors.lastname: Bhutani
authors.forename: Brian
authors.initials: B
authors.lastname: Weston
authors.forename: Wayne
authors.initials: W
authors.lastname: Hofstetter
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.forename: Hironori
authors.initials: H
authors.lastname: Shiozaki
authors.forename: Roopma
authors.initials: R
authors.lastname: Wadhwa
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sudo
authors.forename: Elena
authors.initials: E
authors.lastname: Elimova
authors.forename: Shumei
authors.initials: S
authors.lastname: Song
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.forename: Maosheng
authors.initials: M
authors.lastname: Huang
authors.forename: Jaffer
authors.initials: J
authors.lastname: Ajani
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D014408:Biomarkers, Tumor / Q000235:genetics*; D059248:Chemoradiotherapy; D015331:Cohort Studies; 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; D035683:MicroRNAs / Q000235:genetics*; D020360:Neoadjuvant Therapy; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: chemotherapy; esophageal cancer; miRNA; radiation; response
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