RESUMEN
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%).
Asunto(s)
Biomarcadores de Tumor/genética , Enfermedad de Hodgkin/diagnóstico , Enfermedad de Hodgkin/genética , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/genética , Transducción de Señal/efectos de los fármacos , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/metabolismo , Femenino , Perfilación de la Expresión Génica , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Modelos Estadísticos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasia Residual/diagnóstico , Neoplasia Residual/tratamiento farmacológico , Neoplasia Residual/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Adhesión en Parafina , ARN Mensajero/genética , Inducción de Remisión , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Medición de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
In this paper, authors suggest a model that reflects the role played by the Web site characteristics and the previous level of satisfaction as determinant factors of trust in the Web site. Also, authors consider the moderating effects of consumers' motives and inhibitors to purchase online. Results show that satisfaction with previous purchases, the Web site security and privacy policies, and service quality are the main determinants of trust. Also, the motives and inhibitors the individuals perceive when buying online determine the type of signals they consider to trust.