Development of Noninvasive Biomarkers for Diagnosing and Monitoring Nonindolent Prostate Cancer.

摘要

While prostate cancer (PCa) is the most common solid organ malignancy in men, only 20 30% progress to metastatic disease. Men with indolent disease are offered a treatment plan that involves active surveillance (AS). However, there is a significant risk of under-grading the tumor and repeated invasive biopsies are required. We hypothesized that transcripts associated with high Gleason grade cancers are quantifiable in urine samples from men with prostate cancer, and that measurements of grade-associated transcripts will reflect the presence of higher-grade non-indolent tumors. By gene expression analysis (from microdissected Gleason-pattern (GP) 3 and GP4 PCa), in combination with publically available Gleason-associated transcriptional profiles, we have created a 46-gene panel that differentiates high Gleason from low Gleason grade PCa. Moreover, we have found that up- regulation of several GP-associated transcripts, such as RELN, associate with adverse clinical outcomes. We validated the GP4-associated upregulation of candidate genes by qPCR. Additionally, we have started to measure by qPCR the transcript levels for 6-genes in urine sediments from patients undergoing biopsy. Although, a significant difference exists between negative biopsy and PCa for two genes, no significant differences were found between GS6 and GS 8 biopsies. Urine sediments from patients undergoing radical prostatectomy are necessary to test their accuracy in predicting high versus low grade tumors. The discovery of high grade-associated transcripts in urine from patients with presumed indolent prostate cancer could substantially improve accurate staging of prostate tumors and clinical management decisions.