Oncotarget

Research Papers:

An integrative approach for the identification of prognostic and predictive biomarkers in rectal cancer

Marco Agostini _, Klaus-Peter Janssen, Il-Jin Kim, Edoardo D’Angelo, Silvia Pizzini, Andrea Zangrando, Carlo Zanon, Chiara Pastrello, Isacco Maretto, Maura Digito, Chiara Bedin, Igor Jurisica, Flavio Rizzolio, Antonio Giordano, Stefania Bortoluzzi, Donato Nitti, Salvatore Pucciarelli

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Oncotarget. 2015; 6:32561-32574. https://doi.org/10.18632/oncotarget.4935

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Abstract

Marco Agostini1,2,3, Klaus-Peter Janssen4, ll-Jin Kim5, Edoardo D’Angelo1,2, Silvia Pizzini6, Andrea Zangrando2,7, Carlo Zanon8, Chiara Pastrello9, Isacco Maretto1, Maura Digito1, Chiara Bedin1,3, Igor Jurisica9, Flavio Rizzolio10,11, Antonio Giordano11, Stefania Bortoluzzi12, Donato Nitti1,*, Salvatore Pucciarelli1,*

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

2Istituto di Ricerca Pediatrica-Città della Speranza, Padua, Italy

3The Methodist Hospital Research Institute, Houston, USA

4Department of Surgery, UCSF, San Francisco, CA, USA

5Department of Surgery, UCSF, San Francisco, CA 94143, California, CA

6Department of Biology, University of Padua, Padua, Italy

7Department of Woman and Child Health, University of Padua, Padua, Italy

8Neuroblastoma Laboratory, Istituto di Ricerca Pediatrica-Città della Speranza, Padua, Italy

9Ontario Cancer Institute, the Campbell Family Institute for Cancer Research, and Techna Institute, University Health Network, Toronto, ON, Canada

10Department of Translational Research, National Cancer Institute – CRO-IRCSS, Aviano, Italy

11Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA

12Department of Molecular Medicine, University of Padua, Padua, Italy

*These authors have contributed equally to this work

Correspondence to:

Marco Agostini, e-mail: m.agostini@unipd.it

Keywords: rectal cancer, integrated approach, biological network, prognostic, predictive

Received: April 28, 2015     Accepted: August 20, 2015     Published: September 02, 2015

ABSTRACT

Introduction: Colorectal cancer is the third most common cancer in the world, a small fraction of which is represented by locally advanced rectal cancer (LARC). If not medically contraindicated, preoperative chemoradiotherapy, represent the standard of care for LARC patients. Unfortunately, patients shows a wide range of response rates in which approximately 20% has a complete pathological response, whereas in 20 to 40% the response is poor or absent.

Results: The following specific gene signature, able to discriminate responders’ patients from non-responders, were founded: AKR1C3, CXCL11, CXCL10, IDO1, CXCL9, MMP12 and HLA-DRA. These genes are mainly involved in immune system pathways and interact with drugs traditionally used in the adjuvant treatment of rectal cancer.

Discussion: The present study suggests that new ideas for therapy could be found not only limited to studying genes differentially expressed between the two groups of patients but deepening the mechanisms, associated to response, in which they are involved.

Methods: Gene expression studies performed by: Agostini et al., Rimkus et al. and Kim et al. have been merged through a meta-analysis of the raw data. Gene expression data-sets have been processed using A-MADMAN. Common differentially expressed gene (DEG) were identified through SAM analysis. To further characterize the identified DEG we deeply investigated its biological role using an integrative computational biology approach.


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