Portal de Periódicos da CAPES

Serum miR-125b is a non-invasive predictive biomarker of the pre-operative chemoradiotherapy responsiveness in patients with rectal adenocarcinoma

2016; Impact Journals LLC; Volume: 7; Issue: 19 Linguagem: Inglês

10.18632/oncotarget.8725

1949-2553

Edoardo D’Angelo, Matteo Fassan, Isacco Maretto, Salvatore Pucciarelli, Carlo Zanon, Maura Digito, Massimo Rugge, Donato Nitti, Marco Agostini,

Cancer Immunotherapy and Biomarkers

// Edoardo D'Angelo 1, 2 , Matteo Fassan 3 , Isacco Maretto 1 , Salvatore Pucciarelli 1 , Carlo Zanon 4 , Maura Digito 1 , Massimo Rugge 3 , Donato Nitti 1 , Marco Agostini 1, 2, 5 1 Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy 2 Nanoinspired Biomedicine Laboratory, Institute of Pediatric Research, Fondazione Città della Speranza, Padua, Italy 3 Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy 4 Neuroblastoma Laboratory, Pediatric Research Institute, Città della Speranza, Padua, Italy 5 Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas, USA Correspondence to: Marco Agostini, email: m.agostini@unipd.it Keywords: rectal cancer, microRNA, miR-125b, circulating, pre-operative chemoradiotherapy Received: January 26, 2016 Accepted: March 28, 2016 Published: April 13, 2016 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.