Abstract
Prostate cancer (PCa) is the most commonly diagnosed solid organ cancer in men worldwide. Current diagnosis of PCa includes use of initial prostate specific antigen assay which has a high false positive rate, low specificity, and low sensitivity. The side effects of unnecessary prostate biopsies that healthy men are subjected to, often result in unintended health complications. New PCa biomarkers are being discovered to address this unmet need. Here, we report on the creation of a composite score (Prostac) based on three recently discovered PCa biomarkers, Plasmacytoma Variant Translocation 1 (PVT1) exons 4A, 4B, and 9. Statistical analysis of copy numbers derived from a real-time quantitative polymerase chain (qPCR) reaction - based assay, showed these PCa biomarkers to be linearly separable and significantly over expressed in PCa epithelial cells. We train a supervised learning algorithm using support vector machines to generate a classification hyperplane from which a user-friendly composite score is developed. Cross validation of Prostac using data from prostate epithelial cells (RWPE1) and PCa cells (MDA PCa 2b) accurately classified 100% of PCa cells. Creation of the Prostac score lays the groundwork for clinical trial of its use in PCa diagnosis.
Highlights
Prostate cancer (PCa) is the leading form of cancer in men in the United States, resulting in the second largest number of deaths by cancer in men [1, 2]
We have developed the Prostac score of three non-protein coding RNAs transcribed from Plasmacytoma Variant Translocation 1 (PVT1) exons 4A, 4B, and 9 of the PVT1 gene locus
We found the concentration of PVT1 exons 4A and 9 to be positively correlated across both MDA PCa 2b and
Summary
Prostate cancer (PCa) is the leading form of cancer in men in the United States, resulting in the second largest number of deaths by cancer in men [1, 2]. In 2021, 248,530,930 men are projected to be diagnosed with prostate cancer, 34,130 of whom are expected to die from the disease [1]. The disease disproportionately affects men of African ancestry (moAA) who are not just more likely get the disease and more likely to die from it [1]. An effective way to curb cancer mortality is to detect it early and initiate treatment, yet one of the most widely used screening tests for prostate cancer, prostate specific antigen test (PSA), has a high false positive rate [3,4,5]. The unintended health complications from the side effects of unnecessary prostate biopsies resulting from the high false positive rate of PSA, has spurred a growing interest in new biomarkers. The preferred biomarker is one acquired through noninvasive methods that can more effectively isolate indolent from aggressive forms of PCa, so that commensurate management and treatment protocols can be applied [6, 7]
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