Canadian researchers have tentatively identified urine protein signatures that appear to differentiate aggressive from low-risk prostate tumors.
Canadian researchers have tentatively identified urine protein signatures that appear to differentiate aggressive from low-risk prostate tumors. The findings were recently reported in Nature Communications.
“We discovered liquid biopsies using urine, that allow us to identify aggressive prostate cancers prior to surgery,” said senior study author Thomas Kislinger, PhD, Senior Scientist at the Princess Margaret Cancer Centre and an associate professor at the University of Toronto in Ontario, Canada, in an interview. “We used targeted proteomics to accurately and precisely quantify hundreds of proteins in urine samples to develop these liquid biopsy signatures.”
“This could help us to personalize the treatment of prostate cancer patients,” Dr. Kislinger said.
Determining Gleason scores requires needle biopsy, which can also miss occult tumors and metastasis, and entails a risk of complications for the patient, the researchers noted.
“A fluid-based biomarker would be ideal to spare patients with indolent (slow-growing) disease from unnecessary procedures, while identifying and treating those who would benefit from treatment intensification,” said lead study author Yunee Kim, a PhD student in Dr. Kislinger’s lab.
The study team examined urine samples from a total of 281 men, using selected reaction monitoring mass spectrometry (SRM-MS) proteomics and computational biology (bioinformatics) to quantify 150 proteins and identify liquid-biopsy protein signatures. The 150 proteins were quantified from the first cohort of 74 patients, and 34 prostate cancer biomarker proteins were then quantified in a second, independent cohort of 207 patients.
The data was then analyzed to identify a urine protein signature for aggressive prostate cancer.
The protein signatures “accurately distinguish patients with organ-confined stage pT2 and extracapsular stage pT3 prostate cancers, before radical prostatectomy,” they reported. “Overall, 24 diagnostic candidates (21 overexpressed in cancers) and 14 prognostic ones (2 overexpressed in invasive tumors) were identified.”
The researchers cautioned that “substantial work” is still required before possible clinical adoption. “This will include additional validation in independent patient cohorts, preferably using longitudinally collected samples, and additional assay optimizations,” they wrote.
They called for additional biomarker discovery efforts with analysis of extracellular vesicles and glycosylated proteins.
“The next step will be further studies with urine samples from 1,000 international patients to validate if the biomarkers identified have broader clinical utilities in prostate cancer,” said Dr. Kislinger.