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Researchers From Protagen, Targos, Elsewhere ID Protein Biomarkers for Prostate Inflammation

NEW YORK (GenomeWeb) – Scientists from German firms Protagen and Targos Molecular Pathology, along with academic collaborators, have identified autoantibodies associated with antigens that can be used as non-invasive biomarkers for prostate cancer.

Protagen, based in Dortmund, develops diagnostic tools such as its SeroTag multi-marker assay technology, that aid in developing better therapies and treatment strategies for some of the most severe autoimmune diseases. Targos, based in Kassel, provides clinical biomarker services and collaborates with more than 30 pharmaceutical, biotech, and diagnostic companies in Europe and the US.

For the prostate biomarker study, published this week in PLOS One, both companies collaborated with Helmut Klocker, professor at the Medical University of Innsbruck and the Oncotyrol Center for Personalized Cancer Medicine, and Mark Rubin, professor at Weill Medical College of Cornell University and Targos.

While often non-fatal for many years, the incidence of prostate diseases, such as prostate cancer, prostatic hyperplasia, and prostatitis are on the rise, according to recent studies. In most cases, chronic inflammation seems to be a characteristic driver of disease progression and a contributing factor to false-positive prostate-specific antigen prostate cancer testing.

To decrease the number of false positives, researchers have been searching for easily accessible biomarkers for prostate inflammation. Because of the way that the disease is currently diagnosed and monitored, autoantibodies have proved to be an important type of marker molecule since they are linked to the activity in the immune system.

"We've been working on the role of SPOP [an autoantigen] and its mutations in prostate cancer for quite some time," Rubin said in a statement, "it is really exciting to learn more about the links to the immune system and the appearance of SPOP-specific autoantibodies in patient sera."

The researchers conducted a retrospective study that used samples from a cohort of 70 patients (38 with high inflammation and 32 with low inflammation) from a prostate cancer screening study and samples from 63 patients (33 with high inflammation and 30 with low inflammation patients) from a cross-validation study.

The researchers selected autoantigen proteins to study based on their previous autoantibody screens in prostate cancer and autoimmune disease using Protagen's SeroTag protein array technology, and on published autoantigens found associated with cancer.

Of the nearly 4,000 autoantibodies that were detected in at least one of the patients, they found that the autoantibodies against SPAST and SPOP were the most detectable in high inflammation patients and less detectable in low inflammation patients.

They cross-validated the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array. The researchers found that five autoantibodies were significantly upregulated in the high inflammation group: SPOP, MUT, ZNF671, RAB11B, and CSRP2.

The scientists also evaluated the expression pattern of corresponding autoantigens in malignant and non-malignant prostate tissue to see whether mutations might trigger autoantibodies. For this, they extracted total RNA from both patient groups using Qiagen's AllPrep DNA/RNA Micro Kit, and measured expression using Taqman qPCR assays from Applied Biosystems (Thermo Fisher Scientific). Indeed, they found that antigens of serum-derived autoantibodies are expressed in prostate tissue.

"We were not only able to identify new relevant prostate-specific autoantigens," Klocker said in a statement, "but also show the orthogonal validation of this serum marker on tissue microarrays with our partners at Targos."

The researchers were able to go one step further and identify a biomarker panel consisting of these five serum-derived autoantibodies that has the potential to discriminate between high or low inflammation in prostate cancer patient samples.

"It is always a good cross validation, when two independent methods yield the same result," Targos CEO Thomas Henkel said in a statement. "Validated biomarkers in immune oncology and other immune diseases are a valuable asset."

Protagen CEO Stefan Müllner further stated, "There’s an unmet diagnostic need in prostate cancer diagnostics, and the commercial value of novel, more reliable options that don’t involve biopsies and improve follow-up of patients are very attractive."