Development of a reliable assay to measure glypican-1 in plasma and serum reveals circulating glypican-1 as a novel prostate cancer biomarker

Abstract

Prostate cancer is responsible for hundreds of thousands of annual deaths worldwide. The current gold standard in early detection of prostate cancer, the prostate specific antigen test, boasts a high sensitivity but low specificity, resulting in many unnecessary prostate biopsies. Thus, emphasis has been placed on identifying new biomarkers to improve prostate cancer detection. Glypican-1 has recently been proposed as one such biomarker, however further exploration into its predictive power has been hindered by a lack of available, dependable glypican-1 immunoassays. Previously, we identified human glypican-1 as the antigenic target of the MIL-38 monoclonal antibody. Additionally, we have now generated another monoclonal antibody, 3G5, that also recognizes human glypican-1. Here we report the development of a reliable, custom Luminex® assay that enables precise quantitation of circulating human glypican-1 in plasma and serum. Using this assay, we show for the first time that circulating glypican-1 levels can differentiate non-cancer (normal and benign prostatic hyperplasia) patients from prostate cancer patients, as well as benign prostatic hyperplasia patients alone from prostate cancer patients. Our findings strongly promote future investigation into the use of glypican-1 for early detection of prostate cancer.

Exosomes and GPI-anchored proteins: Judicious pairs for investigating biomarkers from body fluids

“…Exosomal GPC-1 detection was then assessed by different methods as a way to detect pancreatic cancer in patients from plasma samples [146][147][148]. This GPC-1 exosomal feature was also used with patient plasma samples to detect colorectal [149] or prostate [150] cancers, and with urine samples for prostate cancer detection [151].…”

Targeted beta therapy of prostate cancer with 177Lu-labelled Miltuximab® antibody against glypican-1 (GPC-1)

“…However, expression of GPC-1 is not expected in normal tissue [7] and Miltuximab® labelled with 67 Ga has proven safe in first in a human study [16]. Expression of GPC-1 in PCa is well established and correlates with Gleason score [7,8,29], in line with the known role of GPC-1 in tumour growth, invasion and metastasis. Targeting of PSMA with 68 Ga-PSMA-PET and 177 Lu-PSMA or 177 Lu-J591 has shown promise for imaging and therapy of PCa respectively.…”

Circulating Heparan Sulfate Proteoglycans as Biomarkers in Health and Disease

“…4, the vast majority of the selected studies have been focused on two cancer types responsible for immense health care problems, hepatocellular carcinoma and multiple myeloma, which will be discussed below. With regard to other cancer types, readers are referred to ►Table 1 [96][97][98][99][100][101][102][103][104][105][106] and ►Supplementary Table S2, available online only, for the main findings.…”