Clinical utility of a serum biomarker panel in distinguishing prostate cancer from benign prostate hyperplasia

Abstract

Prostate-specific antigen (PSA) screening for prostate cancer (PCa) is limited by the lack of specificity but is further complicated in the benign prostatic hyperplasia (BPH) population which also exhibit elevated PSA, representing a clear unmet need to distinguish BPH from PCa. Herein, we evaluated the utility of FLNA IP-MRM, age, and prostate volume to stratify men with BPH from those with PCa. Diagnostic performance of the biomarker panel was better than PSA alone in discriminating patients with negative biopsy from those with PCa, as well as those who have had multiple prior biopsies (AUC 0.75 and 0.87 compared to AUC of PSA alone 0.55 and 0.57 for patients who have had single compared to multiple negative biopsies, respectively). Of interest, in patients with PCa, the panel demonstrated improved performance than PSA alone in those with Gleason scores of 5–7 (AUC 0.76 vs. 0.56) and Gleason scores of 8–10 (AUC 0.74 vs. 0.47). With Gleason scores (8–10), the negative predictive value of the panel is 0.97, indicating potential to limit false negatives in aggressive cancers. Together, these data demonstrate the ability of the biomarker panel to perform better than PSA alone in men with BPH, thus preventing unnecessary biopsies.

Filamin A Is a Prognostic Serum Biomarker for Differentiating Benign Prostatic Hyperplasia from Prostate Cancer in Caucasian and African American Men

“…All men in the analysis cohort had a PSA in the range of 4-10 ng/mL and a negative digital rectal exam (DRE). Additional clinical characteristics of the study cohort are described in Table 1, also being previously published in [4]. In our previous study, we showed that logistic regression using a panel of FLNA, age, and prostate volume performed better than PSA in discriminating between men with PCa and men with BPH.…”

“…We previously identified the level of a cleaved peptide of Filamin A (FLNA) in serum, when combined with prostate volume and age among men who all had elevated PSA levels between 4 and 10 ng/mL, that provided superior predictive performance compared to PSA in distinguishing between men with BPH and men with PCa [4]. The identified protein, FLNA, has been implicated for its role in PCa metastasis, which supports the biological plausibility that FLNA may be a serum biomarker for a PCa diagnosis [5].…”

Molecular Biomarkers in Cancer

“…Therefore, the current prostate cancer screening program using PSA would not be desirable in a clinical setting, and it would only be recommended for men who express a specific interest in screening [ 132 ]. New tests are under evaluation, such as a recently developed biomarker panel combining filamin-A gene, age, and prostate volume which has a better performance than PSA alone, especially in men with benign hyperplasia [ 133 ].…”

Genome-wide studies in prostate cancer poised liquid biopsy as a molecular discovery tool

“…Liquid biopsies utilizing body fluids such as blood, urine and saliva and analyzing biomaterials in circulation show promise for revolutionizing tumour profiling and monitoring practices. It contributes to understanding the signals determining threshold tumour development ( 6 ), highlights metastatic markers, and provides complementary information for treatment response ( 7 , 8 ). In addition to the biomarker potential, it begins to serve as a method for evaluating mechanisms behind therapy resistance ( 9 ).…”