PURPOSE: This is the first report of the development and performance of a platform that interrogates small noncoding RNAs (sncRNA) isolated from urinary exosomes (the miR Sentinel™ Tests): the Sentinel™ PCa Test, that classifies patients with prostate cancer from subjects with no evidence of prostate cancer, the miR Sentinel™ CS Test, that stratifies patients with prostate cancer between those with low risk prostate cancer (GG1) from those with intermediate and high risk disease (GG2-5), and the miR Sentinel™ HG Test, that stratifies prostate cancer patients between those with low and favorable intermediate risk prostate cancer (GG1 or GG2) versus those with high risk (GG3-5) disease. MATERIALS AND METHODS: sncRNAs were extracted from urinary exosomes of 235 participants and interrogated on miR 4.0 microarrays. Using proprietary Selection and Classification Algorithms, informative sncRNAs were selected to customize an interrogation OpenArray™ platform that forms the basis of the tests. The tests were validated using a case-control sample of 1,436 subjects. RESULTS: The performance of the miR Sentinel™ PCa Test demonstrated sensitivity 94% and specificity 92%. The Sentinel™ CS Test demonstrated a sensitivity of 93% and specificity 90% for prediction of the presence of GG 2 or greater cancer, and the Sentinel™ HG Test demonstrated a sensitivity of 94% and specificity of 96% for the prediction of the presence of GG 3 or greater cancer. CONCLUSIONS: The Sentinel™ PCa, CS and HG Tests, demonstrated high levels of sensitivity and specificity, highlighting the utility of interrogation of urinary exosomal sncRNAs for noninvasively diagnosing and classifying prostate cancer with high precision.
PURPOSE: This is the first report of the development and performance of a platform that interrogates small noncoding RNAs (sncRNA) isolated from urinary exosomes (the miR Sentinel™ Tests): the Sentinel™ PCa Test, that classifies patients with prostate cancer from subjects with no evidence of prostate cancer, the miR Sentinel™ CS Test, that stratifies patients with prostate cancer between those with low risk prostate cancer (GG1) from those with intermediate and high risk disease (GG2-5), and the miR Sentinel™ HG Test, that stratifies prostate cancerpatients between those with low and favorable intermediate risk prostate cancer (GG1 or GG2) versus those with high risk (GG3-5) disease. MATERIALS AND METHODS: sncRNAs were extracted from urinary exosomes of 235 participants and interrogated on miR 4.0 microarrays. Using proprietary Selection and Classification Algorithms, informative sncRNAs were selected to customize an interrogation OpenArray™ platform that forms the basis of the tests. The tests were validated using a case-control sample of 1,436 subjects. RESULTS: The performance of the miR Sentinel™ PCa Test demonstrated sensitivity 94% and specificity 92%. The Sentinel™ CS Test demonstrated a sensitivity of 93% and specificity 90% for prediction of the presence of GG 2 or greater cancer, and the Sentinel™ HG Test demonstrated a sensitivity of 94% and specificity of 96% for the prediction of the presence of GG 3 or greater cancer. CONCLUSIONS: The Sentinel™ PCa, CS and HG Tests, demonstrated high levels of sensitivity and specificity, highlighting the utility of interrogation of urinary exosomal sncRNAs for noninvasively diagnosing and classifying prostate cancer with high precision.
Authors: Manuel Ramirez-Garrastacho; Cristina Bajo-Santos; Jesus Martinez de la Fuente; Maria Moros; Carolina Soekmadji; Kristin Austlid Tasken; Aija Line; Elena S Martens-Uzunova; Alicia Llorente Journal: Br J Cancer Date: 2021-11-22 Impact factor: 7.640