Oncotarget

Research Papers:

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

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

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Oncotarget. 2016; 7:28647-28657. https://doi.org/10.18632/oncotarget.8725

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Abstract

Edoardo D’Angelo1,2, Matteo Fassan3, Isacco Maretto1, Salvatore Pucciarelli1, Carlo Zanon4, Maura Digito1, Massimo Rugge3, Donato Nitti1, Marco Agostini1,2,5

1Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy

2Nanoinspired Biomedicine Laboratory, Institute of Pediatric Research, Fondazione Città della Speranza, Padua, Italy

3Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, Padua, Italy

4Neuroblastoma Laboratory, Pediatric Research Institute, Città della Speranza, Padua, Italy

5Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas, USA

Correspondence to:

Marco Agostini, email: [email protected]

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.


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