Tissue biopsies to diagnose prostate cancer are invasive and they often miss cancer cells, which limits their utility for diagnosis. Scientists from The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, got closer to reaching the goal of a noninvasive urine biopsy that detects cancer-specific changes in RNA and metabolites using RNA deep sequencing and mass spectrometry. The results of their study appeared in February 2020 in the journal Scientific Reports.1
“[This work] certainly is provocative in trying to discern different metabolic pathways that can be used to demonstrate cancer [vs] no cancer,” said Neal Shore, MD, medical director for the Carolina Urologic Research Center, Myrtle Beach, South Carolina, who was not involved in the study. “We could potentially use these types of metabolic pathways to test responses to [prostate cancer] therapeutics.” He thinks this test could also lead to personalized treatments for prostate cancer if particular gene alteration profiles are detected in urine samples.
Levels of prostate-specific antigen (PSA) have been used for more than 30 years for prostate cancer screening and diagnosis.2 However, PSA levels are not very specific. “PSA may not be the right way to detect whether a patient has prostate cancer because patients may have other diseases, such as prostatitis and benign prostate hyperplasia, where PSA levels are also elevated,” explained Ranjan Perera, PhD, associate professor in the department of oncology at Johns Hopkins University School of Medicine, and senior author of the study. “We wanted to take a different approach and look at urine,” he told Cancer Therapy Advisor.
Dr Perera said the research team’s idea was to use urine to capture the cells that shed from the prostate to the urethra. They collected 50 ml of urine in patients with prostate cancer and used samples collected from those with or without benign prostatic disease as controls.
They looked for cancer-specific gene signatures in the cells from each sample and found that 37 genes were upregulated in the prostate cancer samples. Known markers of prostate cancer, such as KLK3, PQBP1, TRIM22, and PSMA3 were increased in urine samples from prostate cancer patients relative to controls.
The cells in the tumor samples had higher expression of cancer pathways, including PI3K/AKT and NF-kB. Gene enrichment analysis showed that several other pathways were upregulated in urine from patients with prostate cancer, including pyruvate metabolism and the TCA cycle, which cancer cells use as a source of energy to divide rapidly.
The observed urine signature closely matched what can be found in prostate cancer tissue. The researchers used RNA-Seq data from 65 prostate cancer patients and healthy controls to compare the gene-expression profile of the exfoliated urine cells to the profile of cells in prostate tissue. They found that 34 of the 37 genes that were upregulated in urine cells were also increased in the prostate cancer samples.
“The major discovery here is that [we were] able to check for the presence or absence [of cancer],” said Dr Perera. The metabolite profile of the prostate cancer samples was largely distinct from profiles from both the normal tissues and those derived from patients with prostatitis and benign prostate hyperplasia — indicating that this urine biopsy could distinguish between those 2 conditions and prostate cancer.