Proteoglycan Assay Shows Potential as Adjunct to PSA Measurement

Jonathan Henderson, MD

A cell-surface proteoglycan found on prostate cancer cells but not normal prostate tissue demonstrated good specificity as a blood test for prostate cancer, results of a preliminary clinical study showed.

Across a PSA range of 4 to 10 ng/mL, the plasma and serum levels of glypican-1 achieved a 79% specificity for prostate cancer when used as an adjunct to PSA measurement. The assay had a sensitivity of 33%, as reported at the 2015 American Urological Association annual meeting.

“Glypican-1 is a newly identified biomarker in prostate cancer,” said Jonathan Henderson, MD, assistant director of Clinical Research at Regional Urology in Shreveport, Louisiana. “Glypican-1 shows significant promise in improving specificity of detection when comparing both prostate cancer to normal plus patients with BPH [benign prostatic hyperplasia], as well as prostate cancer to BPH alone. Its likely clinical use would be as an adjunctive test for patients with elevated PSA.”

Laboratory studies have shown that glypican-1 has a role in regulating signaling of several different growth factors. Studies involving a glypican-1 knockdown in vitro model showed reduced cellular response to growth factors and reduced invasive potential, as well as reduced invasive potential in a xenograft model.

In a proof-of-concept study, a glypican-1 assay demonstrated 71% sensitivity and 73% specificity for distinguishing between prostate cancer (n = 41) versus a control group (n = 47) plus a cohort of men with BPH (n = 37), said Henderson.

Favorable results led to development of a standard ELISA assay that detects glypican-1 in serum, plasma, and urine. The test has a limit of detection of 3.4 pg/mL and limit of quantitation of 7.2 pg/mL. The test has demonstrated good correlation between detection of glypican-1 in serum and plasma, said Henderson.

Investigators at 10 tertiary community centers in the United States conducted a retrospective pilot study to investigate the glypican-1 assay in 345 men aged >50 years, consisting of 115 each with normal prostates, BPH, and prostate cancer. Investigators evaluated the assay alone and in combination with other markers to examine the ability to differentiate among patients with cancerous and noncancerous prostate conditions. PSA testing alone served as the comparator.

The “healthy” arm included men who had PSA values <2 ng/mL (<3 ng/mL if aged >60 years) and a normal digital rectal exam (DRE). The BPH arm consisted of men with pathology confirmed BPH or clinical BPH in association with PSA levels <2 ng/mL (<3 ng/mL if aged >60 years). The prostate cancer group consisted of men who were at least 1 week postbiopsy showing prostate cancer of Gleason score 7 or greater.

The assay results showed that use of a logarithmic cut point of 1.85 for plasma resulted in a sensitivity of 32% and specificity of 79% for prostate cancer. A log cut point of 1.95 for serum yielded a 37% sensitivity and 75% specificity.

“We observed very good correlation between plasma and serum results for glypican-1, with circulating glypican-1 decreasing in prostate cancer,” said Henderson. “Use of the assay as an adjunct to PSA allows for a better outcome for specificity. The PSA results can be used for sensitivity and the glypican-1 result for specificity.”

Shore N, Concepcion R, Saltzstein D, et al. Glypican-1 as a biomarker for prostate cancer. Presented at: 2015 AUA Annual Meeting; May 15-19, 2015; New Orleans, LA. Abstract PII-LBA3.

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