The patented underlying biomarker technology licensed from the University of California for the Proveri diagnostic and prognostic prostate cancer assays is based on two biomarker signatures:

  • 114 prostate stroma biomarkers that are diagnostic for prostate cancer on the gene expression level even if no tumor is present in the tissue sample
  • 15 prostate biomarkers that are prognostic for prostate cancer outcome, i.e. predict who will need aggressive treatment or for whom “watchful waiting” may be indicated

 

 

Specificity

Sensitivity

Accuracy

Diagnostic Marker Set

98%

88%

97%

Prognostic Marker Set

80%

88%

87%

 

 

The functionality of those biomarker sets has been clinically verified using independent patient tissue. The initial identification of the biomarker sets was done on the mRNA level. In the meantime it has been confirmed that the majority of the biomarkers are also detectable on the protein level in prostate tissue samples.

The identification of these biomarker classifiers resulted from the academic work of the two inventors and founders of Proveri Inc. Dan Mercola, M.D., Ph.D and Michael McClelland, Ph.D. on gene expression changes observed in prostate cancer. Amongst other sources their work has been funded by grants from the National Cancer Institute’s (NCI) “Director’s Challenge” and the NCI “Strategic Partnering to Evaluate Cancer Signatures (SPECS)” program. More recently they have also secured grant funding from NCI’s “Early Detection Research Network” and the Department of Defense to continue their research work.

The problem with diagnosis of prostate cancer with biomarkers used for cancer detection in malignant epithelial tumor tissue is that the cancerous tumors may originate by several different genetic alterations (polyclonal disease).  These cancer-causing genetic alterations can differ significantly between individual patients. Therefore a diagnostic test based on a set of tumor markers historically had utility for only a fraction of the patient population. To be able to include the majority of individuals it was necessary to find biomarkers with clinical utility for diagnosis and prognosis independent of the genetic (polyclonal) cancer-causing changes.

The Proveri technology is based on the indication that malignant prostate tumors cause alterations in the activity of specific genes in the surrounding tissue (stroma). These alterations are stable and can be observed independently from the genetic alterations that lead to malignant transformation of the prostate epithelium. Moreover the expression changes in stroma extend a considerable distance (> 3 mm) from the tumor thereby greatly extending the diagnostic and prognostic information content of tissue harvested by clinical biopsies with a needle diameter of 0.89 mm. This effect minimizes the number of false-negative biopsies currently estimated to be greater than 30% of all negative biopsies.  Measuring the alterations in the gene activity in stroma can therefore be used for diagnosis and prognosis.

One set of clinically validated 114 prostate stroma biomarkers for diagnosis show an overall detection accuracy of >97%. The performance of the diagnostic classifier of 114 biomarkers was tested on 364 patient samples (independent from training samples) including 243 tumor-bearing samples and 121 non-tumor samples*.

A separate set of clinically validated 15 prostate stroma biomarkers determine the aggressiveness of tumor with an overall accuracy of >87%. The performance of the prognostic classifier of 15 biomarkers was tested on 49 patient samples (independent from training samples) including 40 from relapse patients and 9 from patients with indolent disease*.

*See publications tab for references to the scientific literature