title: Modeling risk stratification in human cancer.
abstract: BACKGROUND
  Despite huge prognostic promises, gene expression-based survival assessment is rarely used in clinical routine. Main reasons include difficulties in performing and reporting analyses and restriction in most methods to one high-risk group with the vast majority of patients being unassessed. The present study aims at limiting these difficulties by (i) mathematically defining the number of risk groups without any a priori assumption; (ii) computing the risk of an independent cohort by considering each patient as a new patient incorporated to the validation cohort and (iii) providing an open-access Web site to freely compute risk for every new patient.
  
  
  RESULTS
  Using the gene expression profiles of 551 patients with multiple myeloma, 602 with breast-cancer and 460 with glioma, we developed a model combining running log-rank tests under controlled chi-square conditions and multiple testing corrections to build a risk score and a classification algorithm using simultaneous global and between-group log-rank chi-square maximization. For each cancer entity, we provide a statistically significant three-group risk prediction model, which is corroborated with publicly available validation cohorts.
  
  
  CONCLUSIONS
  In constraining between-group significances, the risk score compares favorably with previous risk classifications.
  
  
  BACKGROUND
  Risk assessment is freely available on the Web at https://gliserv.montp.inserm.fr/PrognoWeb/ for personal or test data files. Web site implementation in Perl, R and Apache.
authors.affiliation: INSERM-UM1, U1040, Institut de Recherche en Biothérapie, 34295 Montpellier, France. thierry.reme@inserm.fr
authors.forename: Thierry
authors.initials: T
authors.lastname: Rème
authors.forename: Dirk
authors.initials: D
authors.lastname: Hose
authors.forename: Charles
authors.initials: C
authors.lastname: Theillet
authors.forename: Bernard
authors.initials: B
authors.lastname: Klein
mesh_terms: D000465:Algorithms; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D005260:Female; D020869:Gene Expression Profiling; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D006801:Humans; D015233:Models, Statistical; D009101:Multiple Myeloma / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D009369:Neoplasms / Q000401:mortality*; D011379:Prognosis; D018570:Risk Assessment; D016019:Survival Analysis