A molecular risk score based on four functional pathways for advanced classical Hodgkin lymphoma

نویسندگان

  • Beatriz Sánchez-Espiridión
  • Carlos Montalbán
  • Ángel López
  • Javier Menárguez
  • Pilar Sabín
  • Carmen Ruiz-Marcellán
  • Andrés Lopez
  • Rafael Ramos
  • Jose Rodríguez
  • Araceli Cánovas
  • Carmen Camarero
  • Miguel Canales
  • Javier Alves
  • Reyes Arranz
  • Agustín Acevedo
  • Antonio Salar
  • Sergio Serrano
  • Águeda Bas
  • Jose M. Moraleda
  • Pedro Sánchez-Godoy
  • Fernando Burgos
  • Concepción Rayón
  • Manuel F. Fresno
  • José García Laraña
  • Mónica García-Cosío
  • Carlos Santonja
  • Jose L. López
  • Marta Llanos
  • Manuela Mollejo
  • Joaquín González-Carrero
  • Ana Marín
  • Jerónimo Forteza
  • Ramón García-Sanz
  • Jose F. Tomás
  • Manuel M. Morente
  • Miguel A. Piris
  • Juan F. García
  • Miguel A Piris
چکیده

Despite improvement in the treatment of advanced classical Hodgkin Lymphoma, around 30% relapse or die as result of the disease. Current predictive systems, based on clinical and analytical parameters, fail to identify these high-risk patients accurately. We took a multistep approach to design a quantitative RT-PCR assay to be applied to routine formalin-fixed paraffin-embedded samples, integrating genes expressed either by the tumor cells and their microenvironment. The significance of 30 genes chosen on the basis of previously published data was evaluated in a set of 282 samples (divided into estimation and validation sets) to build a molecular risk score to predict failure. Adequate RT-PCR profiles were obtained from 262 of 282 cases (92.9%). Best predictor genes were integrated into an 11-gene model including four functional pathways (Cell Cycle, Apoptosis, Macrophage Activation and IRF4) able to identify lowand high-risk patients with different rates of 5-year FFS: 74% versus 44.1% in the estimation set (p < 0.0001); and 67.5% vs. 45.0% in the validation set (p = 0.0217). Moreover, this biological 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 FFS probability 25.2%). For personal use only. on October 28, 2017. by guest www.bloodjournal.org From

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A molecular risk score based on 4 functional pathways for advanced classical Hodgkin lymphoma.

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تاریخ انتشار 2010