title: An integrative approach for the identification of prognostic and predictive biomarkers in rectal cancer.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padua, Italy.|Istituto di Ricerca Pediatrica-Città della Speranza, Padua, Italy.|The Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Agostini
authors.affiliation: Department of Surgery Technische Universitaet Muenchen Ismaninger Muenchen, Germany.
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Janssen
authors.affiliation: Department of Surgery, UCSF, San Francisco, CA, USA.
authors.forename: Il-Jin
authors.initials: IJ
authors.lastname: Kim
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padua, Italy.|Istituto di Ricerca Pediatrica-Città della Speranza, Padua, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: D'Angelo
authors.affiliation: Department of Biology, University of Padua, Padua, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pizzini
authors.affiliation: Istituto di Ricerca Pediatrica-Città della Speranza, Padua, Italy.|Department of Woman and Child Health, University of Padua, Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zangrando
authors.affiliation: Neuroblastoma Laboratory, Istituto di Ricerca Pediatrica-Città della Speranza, Padua, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Zanon
authors.affiliation: Ontario Cancer Institute, The Campbell Family Institute for Cancer Research and Techna Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pastrello
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padua, Italy.
authors.forename: Isacco
authors.initials: I
authors.lastname: Maretto
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padua, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Digito
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padua, Italy.|The Methodist Hospital Research Institute, Houston, TX, USA.
authors.forename: Chiara
authors.initials: C
authors.lastname: Bedin
authors.affiliation: Ontario Cancer Institute, The Campbell Family Institute for Cancer Research and Techna Institute, University Health Network, Toronto, ON, Canada.
authors.forename: Igor
authors.initials: I
authors.lastname: Jurisica
authors.affiliation: Department of Translational Research, National Cancer Institute - CRO-IRCSS, Aviano, Italy.|Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA.
authors.forename: Flavio
authors.initials: F
authors.lastname: Rizzolio
authors.affiliation: Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Molecular Medicine, University of Padua, Padua, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Bortoluzzi
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padua, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Nitti
authors.affiliation: Department of Surgical, Oncological and Gastroenterological Sciences, Section of Surgery, University of Padova, Padua, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pucciarelli
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000235:genetics*; D059186:Chemoradiotherapy, Adjuvant; D019295:Computational Biology; D030541:Databases, Genetic; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D018579:Patient Selection; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D012004:Rectal Neoplasms / Q000235:genetics* / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy; D012307:Risk Factors; D016019:Survival Analysis; D018511:Systems Integration; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: biological network; integrated approach; predictive; prognostic; rectal cancer