A Serum miR Signature Specific to Low-Risk Prostate Cancer
Technical Report,01 Sep 2018,31 Aug 2019
University of Illinois Chicago United States
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The goal of this new proposal is to develop a miR panel as a serum marker to identify biopsy-positive prostate cancer PCa patients with a low-risk of harboring aggressive disease. There are several useful pre-treatment risk calculators that use clinical parameters age, biopsy grade, PSA.These calculators accurately identify high-risk patients defined by clinical parameters. However, there is uncertainty with lowintermediate risk patients with only Gleason grade 3 on biopsy and which of these men require curative treatment. To address this unmet need, we previously identified a serum microRNA miR signature that categorized, with extremely high accuracy, a subset of PCa patients with low-risk of harboring aggressive disease. miRs are stable biomarkers resistant to degradation. Our first study used a cohort designed to discover miRs that were differentially present in the pre-surgical sera from a unnatural cohort of 100 PCa patients with either low-grade Gleason grade 3 or 50 high-grade Gleason grade 45 disease. Using 14 miRs we created a combined miR Score which had clear threshold and a negative predictive value of 0.9 to predict the absence of high-grade PCa among the patients. A unique feature of our discovery study that provides confidence in the predictive ability of the miRs is that the entire radical prostatectomy specimen was step-wised sectioned to ensure absence of high-grade tumors in our low-risk group. As well, none of the PCa patients in our high-grade group, which had abundant Gleason 45 tumors, had high levels of the miRs in their serum. Thus were able to perfectly categorize any patient with high serum miR levels as low-grade and low-risk. The experiments in this study were designed to investigate the serum miRs not only as a biomarker, but also potentially as having biological function in PCa. This is distinct from our discovery study because all of the patients for this proposal will be of low to intermediate-risk.
- Medicine and Medical Research