An integrative approach for the identification of prognostic and predictive biomarkers in rectal cancer
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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
Marco Agostini, e-mail: [email protected]
Keywords: rectal cancer, integrated approach, biological network, prognostic, predictive
Received: April 28, 2015 Accepted: August 20, 2015 Published: September 02, 2015
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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