Identification of plasma protein profiles associated with risk groups of prostate cancer patients

Abstract

Purpose Early detection of prostate cancer (PC) using prostate-specific antigen (PSA) in blood reduces PC-death among unscreened men. However, due to modest specificity of PSA at commonly used cut-offs, there are urgent needs for additional biomarkers contributing enhanced risk classification among men with modestly elevated PSA. Experimental design Recombinant antibody microarrays were applied for protein expression profiling of 80 plasma samples from routine PSA-measurements, a priori divided into four risk groups, based on levels of total and %free PSA. Results The results demonstrated that plasma protein profiles could be identified that pinpointed PC (a malignant biomarker signature) and most importantly that showed moderate to high correlation with biochemically defined PC risk groups. Notably, the data also implied that the risk group with mid-range PSA and low %free PSA, a priori known to be heterogeneous, could be further stratified into two subgroups, more resembling the lowest and highest risk groups, respectively. Conclusions and clinical relevance In this pilot study, we have shown that plasma protein biomarker signatures, associated with risk groups of PC, could be identified from crude plasma samples using affinity proteomics. This approach could in the longer perspective provide novel opportunities for improved risk classification of PC patients.

Multiplexed protein profiling by sequential affinity capture

“…Finally, we challenged the DCA concept in a biomarker analysis setup by investigating two different plasma sample sets collected in the context of prostate cancer (Supporting Information Table S2) . Using multiple antibodies for multiplexed first capture enrichment, we found differential profiles primarily for prostate specific antigen (PSA, as expected) as well as for insulin‐like growth factor binding protein 2 (IGFBP2, Fig.…”

The Translational Status of Cancer Liquid Biopsies

“…IMMray™ PanCan-d is currently undergoing a clinical trial to investigate its diagnostic accuracy for detection of pancreatic cancer in high-risk groups (NCT03693378). The antibody microarray technology has potential to be used in diagnostics of other types of cancer and has already been tested to longitudinally monitor sera of patients with breast cancer [323] and to classify patients based on risk for developing prostate cancer [324].…”

“…A successful case of a multianalyte test that also incorporates clinical data is the Stockholm 3 model (STHLM3). This test combines plasma protein biomarkers (PSA, free PSA, intact PSA, hK2, MSMB, MIC1), 232 genetic polymorphisms associated with prostate cancer in earlier studies, and clinical variables to identify high risk prostate cancer at biopsy [324]. STHLM3 was validated in an independent multi-center community cohort of 533 patients scheduled for prostate biopsy [452].…”

Quantitative proteomic analyses in blood: A window to human health and disease

“…These implications extend into the work of therapeutic and prognostic models necessary for in vivo endeavors as well. Biomarkers identified from proteomics approaches like arrays can already be used to stratify potential patients on their disease risk, or how/if they might respond to any given treatment . But what happens to the proteome following treatment by comparison?…”