A 2,555-man study found blood protein patterns associated with prostate cancer risk years before diagnosis, including signals linked to aggressive disease.
Blood samples collected years before diagnosis carried protein patterns associated with later prostate cancer, including aggressive forms of the disease. The Oxford Population Health study points to immune activity, cell interactions, blood vessel growth and cancer related genes as areas for further investigation. Its findings offer biological leads, but the proteins aren’t ready to guide clinical decisions.
Signals appeared years before diagnosis
The researchers analyzed blood from 982 men who later developed prostate cancer and a randomly selected comparison group of 1,573 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). They measured more than 6,000 proteins and followed participants for about 16 years, examining associations with prostate cancer overall and with clinically significant disease.
Twelve proteins were associated with diagnoses made more than 15 years after blood collection. One was GZMK, produced by immune cells involved in recognizing and destroying abnormal cells. The association raises the possibility that immune processes help shape disease risk well before a tumor is diagnosed. It doesn’t establish that GZMK itself prevents cancer or that cancer was present when the samples were taken.
Seven proteins were linked to aggressive prostate cancer. ANKRD1 stood out: its levels were associated with several serious disease outcomes, including cancer that had spread or was ultimately fatal. Other protein signals pointed to cell adhesion, which affects how cells interact with surrounding tissue, and angiogenesis, the formation of blood vessels.
Links to known cancer genes add biological context
The study also found associations involving proteins produced by genes already implicated in prostate cancer, including ERBB3, KRAS and NRAS. These signals were particularly associated with aggressive prostate cancer diagnosed roughly a decade after blood collection. They may help researchers trace biological changes that precede diagnosis, though the results don’t show that cancer had already developed at the time of sampling.
Professor Karl Smith-Byrne of Oxford Population Health said that finding proteins linked to known prostate cancer driver genes in samples collected years before diagnosis offers insight into the disease’s early stages. With genetic evidence, he said, the findings could help identify pathways that might eventually be studied as targets for preventing aggressive disease.
That distinction matters because prostate cancer includes diseases with very different courses. Some tumors grow slowly and may never cause harm, while others spread and can be life-threatening. First author Zhe Huang said that comparing protein profiles years before diagnosis could help researchers understand how men who later develop aggressive cancer differ from those who do not, and potentially improve future risk assessment.
Promising associations still need validation
The team compared its results with other large population studies and genetic evidence. Some associations received support from those analyses, while others did not. The findings identify candidates for further study; they don’t establish a screening test or show that measuring these proteins would improve clinical prediction.
Most associations were modest, and the researchers said further validation and mechanistic work are needed. Studies that combine tumor genomics with circulating protein measurements could clarify how blood protein levels relate to genetic changes in tumors and to disease development. Dedicated prediction studies would then be needed to determine whether the signals add useful information for identifying men at risk of clinically significant cancer.
The work, part funded by Cancer Research UK, was published in European Urology under the title “Circulating Immune and Cancer Driver Gene Biomarkers Precede Prostate Cancer Diagnosis by over 10yr” and presented at the American Society of Human Genetics (ASHG) Annual Meeting. The researchers described it as the largest population based investigation of protein risk factors for prostate cancer to date.
The next step is better risk prediction
Prostate cancer is the most commonly diagnosed cancer in men worldwide, yet researchers still have limited ways to predict who will develop clinically significant disease. Age and inherited genetics are established risk factors, but they can’t be changed, and preventive options remain limited. Earlier work had identified possible protein risk factors; this larger analysis expands the search across thousands of circulating proteins.
Oxford Population Health Professor Ruth Travis said that measuring many proteins in long-running population studies lets researchers examine biological changes years before diagnosis. The next phase, through the Prostate Cancer Aetiology and Prevention Programme (PCAP), funded by Cancer Research UK, will investigate whether these findings can contribute to improved prediction or prevention.
For now, the study’s clearest contribution is a set of biological leads, including immune and cancer gene related signals, that can be tested in future research. Whether any of them can distinguish aggressive disease early enough to change care remains an open question.
The post Proteins Circulating in Blood Linked to Future Risk of Prostate Cancer appeared first on GEN - Genetic Engineering and Biotechnology News.
Discussion
Sign in to join the discussion.