title: Serum miR-125b is a non-invasive predictive biomarker of the pre-operative chemoradiotherapy responsiveness in patients with rectal adenocarcinoma.
abstract: BACKGROUND
  Therapeutic management of Locally Advanced Rectal Cancer (LARC) involves pre-operative chemoradiotherapy (pCRT) followed by surgery. However, after pCRT the complete pathological response is approximately 20%, whereas in 20 to 40% of patients the response is poor or absent.
  
  
  METHODS
  Cancer biopsy specimens (n= 38) and serum samples (n= 34) obtained before pCRT from 38 LARC patients were included in the study. Patients were classified in responders (R, tumor regression grade [TRG] 1-2; n= 16) and non-responders (NR, TRG 3-5; n= 22) according to the pathological response observed upon surgery. We performed miRNA microarrays analysis on biopsy specimens, and validated the selected candidates both by qRT-PCR (tissue and serum) and by in situ hybridization (tissue, miR-125b) analyses.
  
  
  RESULTS
  Eleven miRNAs were significantly different between R and NR (miR-154, miR-409-3p, miR-127-3p, miR-214*, miR-299-5p and miR-125b overexpressed in NR; miR-33a, miR-30e, miR-338-3p, miR-200a and miR-378 decreased). In particular, miR-125b resulted to be the best candidate to discriminate the two groups (AUC of 0.9026; 95% CI, 0.7618-1.043). Additionally, miR-125b serum levels were significantly overexpressed in NR patients compared to R (p-value=0.0087), with an excellent discriminating power (AUC of 0.782; 95% CI, 0.6123-0.9518).
  
  
  CONCLUSIONS
  The obtained results further support the clinical impact of miRNA analysis. High miR-125b expression in tissue and serum were associated with a poor treatment response in LARC patients, therefore miR-125b could be considered as a possible novel non-invasive biomarker of response in LARC treatment.
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy.|Nanoinspired Biomedicine Laboratory, Institute of Pediatric Research, Fondazione Città della Speranza, Padua, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: D'Angelo
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy.
authors.forename: Isacco
authors.initials: I
authors.lastname: Maretto
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pucciarelli
authors.affiliation: Neuroblastoma Laboratory, Pediatric Research Institute, Città della Speranza, Padua, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Zanon
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Digito
authors.affiliation: Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy.|Nanoinspired Biomedicine Laboratory, Institute of Pediatric Research, Fondazione Città della Speranza, Padua, Italy.|Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Agostini
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics* / Q000628:therapy; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D059248:Chemoradiotherapy; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D057234:Preoperative Period; D012004:Rectal Neoplasms / Q000097:blood / Q000235:genetics* / Q000628:therapy; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C531888:MIRN125 microRNA, human; D035683:MicroRNAs
keywords: circulating; miR-125b; microRNA; pre-operative chemoradiotherapy; rectal cancer