Predictive role of microRNA-related genetic polymorphisms in the pathological complete response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients
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Eva Dreussi1, Salvatore Pucciarelli2, Antonino De Paoli3, Jerry Polesel4, Vincenzo Canzonieri5, Marco Agostini2,6,7, Maria Luisa Friso8, Claudio Belluco9, Angela Buonadonna10, Sara Lonardi11, Chiara Zanusso1, Elena De Mattia1, Giuseppe Toffoli1 and Erika Cecchin1
1 Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
2 Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padua, Italy
3 Radiation Oncology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
4 Epidemiology and Biostatistics, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
5 Pathology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
6 Nano Inspired Biomedicine Laboratory, Istituto di Ricerca Pediatrica, Città della Speranza, Padua, Italy
7 Department of Nanomedicine, The Methodist Hospital Research Institute, Houston, Texas, USA
8 Radiation Oncology, Istituto Oncologico Veneto, IRCCS, Padova, Italy
9 Surgical Oncology, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
10 Medical Oncology B, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
11 Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
Giuseppe Toffoli, email:
Antonino De Paoli, email:
Keywords: microRNA, polymorphisms, rectal cancer, neoadjuvant therapy
Received: November 13, 2015 Accepted: February 16, 2016 Published: February 26, 2016
In rectal cancer, a pathologic complete response (pCR) to pre-operative treatment is a favourable prognostic marker, but is reported in a minority of the patients. We aimed at identifying microRNA-related host genetic polymorphisms predictive of pCR.
A panel of 114 microRNA-related tagging polymorphisms was selected and analyzed on 265 locally advanced rectal cancer patients treated with neoadjuvant chemo-radiotherapy. Patients were stratified in two subgroups according to the radiotherapy dose (50.4Gy for 202 patients, 55.0Gy for 78 patients). Interactions among genetic and clinical-pathological variants were investigated by recursive partitioning analysis.
Only polymorphisms with a consistent significant effect in the two subgroups of patients were selected as predictive markers of pCR. The results were validated by bootstrap analysis. SMAD3-rs744910, SMAD3-rs745103, and TRBP-rs6088619 were associated to an increased chance of pCR (p=0.0153, p=0.0471, p=0.0125). DROSHA-rs10719 and SMAD3-rs17228212 had an opposite detrimental effect on pathological tumour response (p=0.0274, p=0.0049). Recursive partitioning analysis highlighted that a longer interval time between the end of radiotherapy and surgery increases the chance of pCR in patients with a specific combination of SMAD3-rs744910 and TRBP-rs6088619 genotypes.
This study demonstrated that microRNA-related host genetic polymorphisms can predict pCR to neo-adjuvant chemo-radiotherapy, and could be used to personalize the interval time between the end of radiotherapy and surgery.
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