title: A specific miRNA signature correlates with complete pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer.
abstract: OBJECTIVE
  MicroRNAs (miRNAs) are small, noncoding RNA molecules that can be down- or upregulated in colorectal cancer and have been associated to prognosis and response to treatment. We studied miRNA expression in tumor biopsies of patients with rectal cancer to identify a specific "signature" correlating with pathological complete response (pCR) after neoadjuvant chemoradiotherapy.
  
  
  METHODS
  A total of 38 T3-4/N+ rectal cancer patients received capecitabine-oxaliplatin and radiotherapy followed by surgery. Pathologic response was scored according to the Mandard TRG scale. MiRNA expression was analyzed by microarray and confirmed by real-time Reverse Transcription Polymerase Chain Reaction (qRT-PCR) on frozen biopsies obtained before treatment. The correlation between miRNA expression and TRG, coded as TRG1 (pCR) vs. TRG >1 (no pCR), was assessed by methods specifically designed for this study.
  
  
  RESULTS
  Microarray analysis selected 14 miRNAs as being differentially expressed in TRG1 patients, and 13 were confirmed by qRT-PCR: 11 miRNAs (miR-1183, miR-483-5p, miR-622, miR-125a-3p, miR-1224-5p, miR-188-5p, miR-1471, miR-671-5p, miR-1909∗, miR-630, miR-765) were significantly upregulated in TRG1 patients, 2 (miR-1274b, miR-720) were downexpressed. MiR-622 and miR-630 had a 100% sensitivity and specificity in selecting TRG1 cases.
  
  
  CONCLUSIONS
  A set of 13 miRNAs is strongly associated with pCR and may represent a specific predictor of response to chemoradiotherapy in rectal cancer patients.
authors.affiliation: Department of Molecular and Clinical Endocrinology and Oncology, University of Naples Federico II, Naples, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Della Vittoria Scarpati
authors.forename: Francesca
authors.initials: F
authors.lastname: Falcetta
authors.forename: Chiara
authors.initials: C
authors.lastname: Carlomagno
authors.forename: Paolo
authors.initials: P
authors.lastname: Ubezio
authors.forename: Sergio
authors.initials: S
authors.lastname: Marchini
authors.forename: Alfonso
authors.initials: A
authors.lastname: De Stefano
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Singh
authors.forename: Maurizio
authors.initials: M
authors.lastname: D'Incalci
authors.forename: Sabino
authors.initials: S
authors.lastname: De Placido
authors.forename: Stefano
authors.initials: S
authors.lastname: Pepe
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001706:Biopsy; D000069287:Capecitabine; D059186:Chemoradiotherapy, Adjuvant / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000032:analysis*; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012334:RNA, Neoplasm / Q000032:analysis*; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012007:Rectum / Q000737:chemistry / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D009944:Organoplatinum Compounds; D012334:RNA, Neoplasm; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil