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

Marco Agostini, Klaus Peter Janssen, Ll 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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)32561-32574
Number of pages14
JournalOncotarget
Volume6
Issue number32
DOIs
Publication statusPublished - 2015

Keywords

  • Biological network
  • Integrated approach
  • Predictive
  • Prognostic
  • Rectal cancer

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Agostini, M., Janssen, K. P., Kim, L. J., D'Angelo, E., Pizzini, S., Zangrando, A., Zanon, C., Pastrello, C., Maretto, I., Digito, M., Bedin, C., Jurisica, I., Rizzolio, F., Giordano, A., Bortoluzzi, S., Nitti, D., & Pucciarelli, S. (2015). An integrative approach for the identification of prognostic and predictive biomarkers in rectal cancer. Oncotarget, 6(32), 32561-32574. https://doi.org/10.18632/oncotarget.4935