title: Immunological network signatures of cancer progression and survival.
abstract: BACKGROUND
  The immune contribution to cancer progression is complex and difficult to characterize. For example in tumors, immune gene expression is detected from the combination of normal, tumor and immune cells in the tumor microenvironment. Profiling the immune component of tumors may facilitate the characterization of the poorly understood roles immunity plays in cancer progression. However, the current approaches to analyze the immune component of a tumor rely on incomplete identification of immune factors.
  
  
  METHODS
  To facilitate a more comprehensive approach, we created a ranked immunological relevance score for all human genes, developed using a novel strategy that combines text mining and information theory. We used this score to assign an immunological grade to gene expression profiles, and thereby quantify the immunological component of tumors. This immunological relevance score was benchmarked against existing manually curated immune resources as well as high-throughput studies. To further characterize immunological relevance for genes, the relevance score was charted against both the human interactome and cancer information, forming an expanded interactome landscape of tumor immunity. We applied this approach to expression profiles in melanomas, thus identifying and grading their immunological components, followed by identification of their associated protein interactions.
  
  
  RESULTS
  The power of this strategy was demonstrated by the observation of early activation of the adaptive immune response and the diversity of the immune component during melanoma progression. Furthermore, the genome-wide immunological relevance score classified melanoma patient groups, whose immunological grade correlated with clinical features, such as immune phenotypes and survival.
  
  
  CONCLUSIONS
  The assignment of a ranked immunological relevance score to all human genes extends the content of existing immune gene resources and enriches our understanding of immune involvement in complex biological networks. The application of this approach to tumor immunity represents an automated systems strategy that quantifies the immunological component in complex disease. In so doing, it stratifies patients according to their immune profiles, which may lead to effective computational prognostic and clinical guides.
authors: Department of Tumor Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. trevor.clancy@rr-research.no
authors: Trevor
authors: T
authors: Clancy
authors: Marco
authors: M
authors: Pedicini
authors: Filippo
authors: F
authors: Castiglione
authors: Daniele
authors: D
authors: Santoni
authors: Vegard
authors: V
authors: Nygaard
authors: Timothy J
authors: TJ
authors: Lavelle
authors: Mikael
authors: M
authors: Benson
authors: Eivind
authors: E
authors: Hovig
mesh_terms: D019985:Benchmarking; D019295:Computational Biology / Q000379:methods*; D018450:Disease Progression; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm / Q000235:genetics / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009928:Organ Specificity; D011379:Prognosis; D015996:Survival Rate