Cell Surface Amino Acid Potential as Prostate Cancer Biomarker

Wayne Kuznar

August 2015, Vol 6, No 7 - Personalized Medicine


New Orleans, LA—Prostate cancer may soon have a new biomarker. The cell surface amino acid glypican-1 (GPC-1) was shown in a pilot study to have specificity of >70% for prostate cancer with a sensitivity of >30%, said Jonathan Henderson, MD, a urologist at Regional Urology in Shreveport, LA, at the 2015 American Urological Association meeting.

It will most likely be used as an adjunctive test for patients with an elevated level of prostate-specific antigen (PSA), said Dr Henderson.

“The take-home message we found with this test is that clinical utility is a high specificity,” he said. “We think we can use the PSA result for the sensitivity that it gives us, but then fine tune it with GPC-1, with the specificity demonstrated at 79% for prostate cancer patients.”

GPC-1 is a 558 amino acid–linked proteoglycan that occurs on the cell wall of prostate tissue. It functions as a co­receptor that regulates growth factor signaling. In preclinical studies, a monoclonal antibody (MIL-38) was developed that binds GPC-1. A proof-of-concept study using urine samples showed a sensitivity of 71% and a specificity of 73% in discriminating between prostate cancer tissue and normal tissue. An enzyme-linked immunosorbent assay kit (MiCheck) that detects GPC-1 in serum, plasma, and urine was then developed.

The objectives of the pilot study were to investigate the range of GPC-1 in normal tissue, benign tissue, and malignant tissue. The study included 3 arms, each with 115 patients:

  • Arm 1, the healthy arm with a normal digital rectal examination, included men aged >50 years with a PSA <2 ng/mL (<3 ng/mL for men aged ≥60 years)
  • Arm 2 enrolled men with pathologically confirmed benign prostatic hyperplasia (BPH) or clinical BPH if PSA was in the normal range
  • Arm 3 was comprised of men with prostate cancer who were ≥1 weeks postbiopsy and had a Gleason score of ≥7 to include only significant cancer.
The study was run by the CUSP research consortium across 10 tertiary community sites in the United States.

Very good correlation was found between plasma and serum for GPC-1, with circulating GPC-1 declining in prostate cancer, thereby significantly differentiating normal and benign tissue from prostate cancer (P = .035 for plasma and P = .034 for serum).

Various GPC-1 cut points were assessed to maximize specificity. Specific­ity was maximized at the cut points of 1.85 log in plasma and 1.95 log in serum to permit the test’s use as an adjunctive test to PSA to allow a better outcome for specificity. The specificity was 79% in plasma and 75% in serum for prostate cancer, with sensitivity rates of 32% and 37%, respectively. For patients with prostate cancer and a PSA level of 4 ng/mL to 10 ng/mL, specificity was 79% and sensitivity was 33%.

“GPC-1 shows significant promise in improving specificity, comparing prostate cancer to benign tissues,” said Dr Henderson. “The clinical use of this molecule will likely be as an adjunctive test in patients who have an elevated PSA, specifically in that gray zone between 4 ng/mL and 10 ng/mL.”

Dr Henderson said that a pivotal trial of 1200 patients is planned that will also use the CUSP consortium.