title: A molecular risk score based on 4 functional pathways for advanced classical Hodgkin lymphoma.
abstract: Despite improvement in the treatment of advanced classical Hodgkin lymphoma, approximately 30% of patients relapse or die as result of the disease. Current predictive systems, determined by clinical and analytical parameters, fail to identify these high-risk patients accurately. We took a multistep approach to design a quantitative reverse-transcription polymerase chain reaction assay to be applied to routine formalin-fixed paraffin-embedded samples, integrating genes expressed by the tumor cells and their microenvironment. The significance of 30 genes chosen on the basis of previously published data was evaluated in 282 samples (divided into estimation and validation sets) to build a molecular risk score to predict failure. Adequate reverse-transcription polymerase chain reaction profiles were obtained from 262 of 282 cases (92.9%). Best predictor genes were integrated into an 11-gene model, including 4 functional pathways (cell cycle, apoptosis, macrophage activation, and interferon regulatory factor 4) able to identify low- and high-risk patients with different rates of 5-year failure-free survival: 74% versus 44.1% in the estimation set (P < .001) and 67.5% versus 45.0% in the validation set (P = .022). This model can be combined with stage IV into a final predictive model able to identify a group of patients with very bad outcome (5-year failure-free survival probability, 25.2%).
authors.affiliation: Molecular Pathology Programme, Genetic and Molecular Epidemiology Group, Tumour Bank, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sánchez-Espiridión
authors.forename: Carlos
authors.initials: C
authors.lastname: Montalbán
authors.forename: Angel
authors.initials: A
authors.lastname: López
authors.forename: Javier
authors.initials: J
authors.lastname: Menárguez
authors.forename: Pilar
authors.initials: P
authors.lastname: Sabín
authors.forename: Carmen
authors.initials: C
authors.lastname: Ruiz-Marcellán
authors.forename: Andrés
authors.initials: A
authors.lastname: Lopez
authors.forename: Rafael
authors.initials: R
authors.lastname: Ramos
authors.forename: Jose
authors.initials: J
authors.lastname: Rodríguez
authors.forename: Araceli
authors.initials: A
authors.lastname: Cánovas
authors.forename: Carmen
authors.initials: C
authors.lastname: Camarero
authors.forename: Miguel
authors.initials: M
authors.lastname: Canales
authors.forename: Javier
authors.initials: J
authors.lastname: Alves
authors.forename: Reyes
authors.initials: R
authors.lastname: Arranz
authors.forename: Agustín
authors.initials: A
authors.lastname: Acevedo
authors.forename: Antonio
authors.initials: A
authors.lastname: Salar
authors.forename: Sergio
authors.initials: S
authors.lastname: Serrano
authors.forename: Agueda
authors.initials: A
authors.lastname: Bas
authors.forename: Jose M
authors.initials: JM
authors.lastname: Moraleda
authors.forename: Pedro
authors.initials: P
authors.lastname: Sánchez-Godoy
authors.forename: Fernando
authors.initials: F
authors.lastname: Burgos
authors.forename: Concepción
authors.initials: C
authors.lastname: Rayón
authors.forename: Manuel F
authors.initials: MF
authors.lastname: Fresno
authors.forename: José García
authors.initials: JG
authors.lastname: Laraña
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Cosío
authors.forename: Carlos
authors.initials: C
authors.lastname: Santonja
authors.forename: Jose L
authors.initials: JL
authors.lastname: López
authors.forename: Marta
authors.initials: M
authors.lastname: Llanos
authors.forename: Manuela
authors.initials: M
authors.lastname: Mollejo
authors.forename: Joaquín
authors.initials: J
authors.lastname: González-Carrero
authors.forename: Ana
authors.initials: A
authors.lastname: Marín
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Forteza
authors.forename: Ramón
authors.initials: R
authors.lastname: García-Sanz
authors.forename: Jose F
authors.initials: JF
authors.lastname: Tomás
authors.forename: Manuel M
authors.initials: MM
authors.lastname: Morente
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.forename: Juan F
authors.initials: JF
authors.lastname: García
mesh_terms: D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D018365:Neoplasm, Residual / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016612:Paraffin Embedding; D012333:RNA, Messenger / Q000235:genetics; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger