ArticlesA whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer: a prospective study
Introduction
Castration-resistant prostate cancer is a strikingly heterogeneous disease state that affects patients with varying metastatic burden and symptoms.1 As a result of this heterogeneity, the overall survival of patients with castration-resistant prostate cancer can be extremely variable, ranging from several months to several years. The ability to accurately predict prognosis in men with castration-resistant prostate cancer is crucial to assist with patient counselling and to optimise clinical-trial design and patient stratification.
Several studies have correlated clinical and laboratory variables, including age, functional status, extent of bone and other metastases, prostate-specific antigen (PSA), alkaline phosphatase, and lactate dehydrogenase, with survival in patients with castration-resistant prostate cancer.2, 3, 4 Additionally, points-based nomograms have been developed combining these variables.5, 6 While such nomograms have improved the ability to individualise prognosis, they offer only moderate predictive discrimination, highlighting the need for improved models.
Interactions between blood cells and the peripheral tissue through which blood circulates, including neoplastic tissue, might alter the gene expression of blood cells. Indeed, recent studies have shown that gene-expression profiling of peripheral blood cells could yield diagnostic and prognostic information regarding various disease states.7, 8, 9, 10 Expression profiling of blood offers several practical advantages compared with expression profiling of tumour tissue, including the minimally invasive nature of sample acquisition, relative ease of standardisation of sampling protocols, and the ability to obtain repeated samples over time. In this study, we tested the hypothesis that transcriptional profiling of whole blood could yield prognostic information in men with astration-resistant prostate cancer.
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Patient population
The training set comprised 62 patients with castration-resistant prostate cancer, with or without the presence of radiographic metastases, and on various treatment regimens, enrolled at the Dana-Farber Cancer Institute from August, 2006, to June, 2008, on a genitourinary oncology clinical database and biorepository protocol. Whole-blood samples were prospectively collected in PAXgene Blood RNA tubes (PreAnalytiX, Hombrechtikon, Switzerland) from patients in this cohort. The validation set
Results
The baseline characteristics of patients in the training set and validation set were similar, though a slightly higher proportion of patients in the validation set had received previous chemotherapy (table 1).
Blood samples were available from all 62 patients in the training set for gene-expression profiling. As of June 20, 2008, a total of 47 patients in the training set were alive and 15 (24%) had died. All 168 target genes and all pairs of these genes were entered directly as predictors in
Discussion
The prognosis of patients with castration-resistant prostate cancer is extremely heterogeneous and the ability to predict prognosis has been limited by models with only moderate predictive discrimination. We postulated that gene-expression profiling of whole blood, which might be influenced by neoplastic tissue through which blood circulates, could provide insights into the behaviour of malignant disease. Indeed, the peripheral-blood six-gene model was capable of predicting survival in patients
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RWR and MG contributed equally to this report