Identification of a candidate gene panel for the early diagnosis of prostate cancer
A partir d'échantillons d'urine et de biopsies prélevés sur 358 patients présentant un niveau sérique élevé du PSA, cette étude identifie un biomarqueur, basé sur les niveaux urinaires de 3 gènes (HOXC6, TRD1 et DLX1), permettant de prédire le score de Gleason
Purpose: Serum PSA (sPSA) testing has led to the identification of patients with indolent prostate cancer (PCa) and inevitably overtreatment has become a concern. Progensa® PCA3 urine testing was shown to improve the diagnosis of PCa, but its diagnostic value for aggressive PCa is limited. Therefore, urinary biomarkers that can be used for prediction of Gleason score ≥7 PCa in biopsies are urgently needed.
Experimental Design: Using gene expression profiling data, 39 PCa biomarkers were identified. After qPCR analysis on tissue specimens and urinary sediments, 8 promising biomarkers for the urinary detection of PCa were selected (ONECUT2, HOXC4, HOXC6, DLX1, TDRD1, NKAIN1, MS4A8B, PPFIA2). The hypothesis that biomarker combinations improve the diagnostic value for aggressive PCa was tested on 358 urinary sediments of an intention-to-treat cohort.
Results: A urinary 3-gene panel (HOXC6, TDRD1 and DLX1) had higher accuracy (AUC 0.77; 95% CI 0.71-0.83) to predict Gleason score ≥7 PCa in biopsies compared with Progensa® PCA3 (AUC 0.68; 95% CI 0.62-0.75) or sPSA (AUC 0.72; 95% CI 0.65-0.78). Combining the 3-gene panel with sPSA further improved the predictive accuracy (AUC 0.81; 95% CI 0.75-0.86). The accuracy of the 3-gene predictive model was maintained in subgroups with low sPSA concentrations.
Conclusions: The urinary 3-gene panel (HOXC6, TDRD1 and DLX1) represents a promising tool to identify patients with aggressive PCa, also in those with low serum PSA values. The combination of the urinary 3-gene panel with sPSA bears great potential for the early diagnosis of patients with clinically significant PCa.
Clinical Cancer Research , résumé, 2015