Protein Biomarker Increases Sensitivity of a Urine-based Prostate Cancer Test

By LabMedica International staff writers
Posted on 05 May 2021
A team of British researchers increased the sensitivity of an advanced RNA and DNA biomarker-based urine test for diagnosis of aggressive prostate cancer by including the measurement of a protein biomarker, which is expected to reduce the number of unnecessary biopsies performed every year by up to 35%.

Prostate cancer exhibits extreme clinical heterogeneity; 10‐year survival rates following diagnosis approach 84%, yet prostate cancer is still responsible for 13% of all cancer deaths in men in the United Kingdom. Current practice assesses a patient's disease using a PSA (prostate specific antigen) blood test, prostate biopsy, and MRI. However, up to 60% of men with a raised PSA level are negative for prostate cancer on biopsy.

Image: EN2: a novel prostate cancer biomarker (Photo courtesy of Future Medicine)

Coupled with the high rates of diagnosis, prostate cancer is more often a disease that men die with rather than from. This illustrates the urgent need for clinical tools able to selectively identify those men with cancers that only require monitoring from those men harboring a disease that requires intervention.

Recently, investigators at the University of East Anglia (Norwich, United Kingdom) developed a multivariable risk prediction model called ExoMeth by integrating clinical, urine‐derived cell‐free messenger RNA (cf‐RNA) and urine cell DNA methylation data capable of noninvasively detecting significant prostate cancer in patients in lieu of biopsy.

In the current study, the investigators extended this approach by developing a urine test that not only predicted whether a patient had prostate cancer but also indicated how aggressive the disease was. This model (ExoGrail) combined the measurement of the protein-marker Engrailed-2 (EN2) and the levels of 10 genes measured in urine.

EN2 is a homeodomain-containing transcription factor that has an essential function in early development, which in mammals includes the delineation of the midbrain/hindbrain border. For a transcription factor it has a number of unusual properties, including the ability to be secreted from cells and taken up by others. Indeed, a recent study indicated that prostate cancer cells can secrete EN2 protein through vesicles which are then taken up by other non-EN2 expressing cells, where it can directly influence the transcription of target genes. The secretory behavior of EN2 makes it a potential biomarker for prostate cancer, and indeed EN2 protein can be detected in the urine of men with prostate tumors. The original and subsequent studies have generally supported a diagnostic role for urinary EN2, including a relationship between urinary EN2 concentration and tumor volume. More recently, a lateral flow-based test for EN2 has been described that could potentially allow point-of-care testing.

During the current study, the investigators used the new ExoGrail test to analyze urine samples from 207 patients who had undergone prostate cancer biopsy. Results revealed that the test identified which patients had prostate cancer and which did not. Furthermore, the ExoGrail test provided risk scores for patients and highlighted those for which an invasive biopsy would have been beneficial.

Senior author Dr. Dan Brewer, senior lecturer in cancer studies at the University of East Anglia, said, "While prostate cancer is responsible for a large proportion of all male cancer deaths, it is more commonly a disease men die with rather than from.

Therefore, there is a desperate need for improvements in diagnosing and predicting outcomes for prostate cancer patients to minimize over-diagnosis and over treatment whilst appropriately treating men with aggressive disease, especially if this can be done without taking an invasive biopsy. Invasive biopsies come at considerable economic, psychological, and societal cost to patients and healthcare systems alike. Our new urine test not only shows whether a patient has prostate cancer, but it importantly shows how aggressive the disease is. This allows patients and doctors to select the correct treatment. And it has the potential to reduce the number of unnecessary biopsies by 35%."

The ExoGrail urine test for detection of prostate cancer was described in the April 27, 2021, online edition of the journal Cancers.

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University of East Anglia


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