Abstract 2196: Serum Filamin A is a prognostic biomarker for screening benign prostatic hyperplasia vs prostate cancer in Caucasian and African American men

Abstract

Abstract Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges pose major issues with identification of indolent and or aggressive cancers. Prostate cancer screening is driven by prostate specific antigen (PSA), however, PSA’s screening utility is diminished in men with benign prostatic hyperplasia (BPH) due to an enlarged prostate and elevated PSA, triggering unnecessary biopsies in men with this condition. Thus, there is a critical unmet medical need to identify a marker for men with these conditions. Moreover, it is crucial to test any novel biomarker in populations of different ancestry (especially African American men who have higher prostate cancer risk) to ensure results apply regardless of race. To this extent, we recently identified a cleaved fragment of Filamin A (FLNA) protein (as measured by IP-MRM mass spectrometry assessment) as a novel biomarker for stratifying BPH from prostate cancer and subsequently evaluated its utility in Caucasian and African American patients. The men had a negative digital rectal examination (DRE), PSA between 4-10 ng/ml and all underwent prostate biopsy. In African American (AA) men, FLNA expression exhibited diagnostic utility for stratifying BPH from all prostate cancer patients (0.72 AUC, 0.82 PPV, 0.76 NPV, 14.2 OR, P Value - 1.5 e-08 in 48 BPH and 139 PCa AA men) and outperformed PSA (0.54 AUC, 0.75 PPV, 0.28 NPV, 1.1 OR, P Value 0.78). In addition, FLNA could stratify BPH from Gleason 7-10 prostate cancers (0.71 AUC, 0.66 PPV, 0.86 NPV, 12.2 OR, P Value 1.7 e-05 in 48 BPH and 60 PCa AA men) and again outperformed PSA (0.5 AUC, 0.58 PPV, 0.62 NPV, 2.18 OR, P Value 0.24). In Caucasian American (CA) men, FLNA expression exhibited diagnostic utility for stratifying BPH from all prostate cancer patients (0.68 AUC, 0.68 PPV, 0.73 NPV, 5.6 OR, P Value 1.6 e-12 in 191 BPH and 281 PCa CA men) and outperformed PSA (0.56 AUC, 0.58 PPV, 0.28 NPV, 0.55 OR, P Value 0.13). FLNA could also stratify BPH from Gleason 7-10 prostate cancers (0.74 AUC, 0.46 PPV, 0.96 NPV, 19.4 OR, P Value 1.6 e-12 in 119 BPH and 109 PCa CA men) and again outperformed PSA (0.46 AUC, 0.35 PPV, 0.38 NPV, 0.32 OR, P Value 0.03). Previously we showed FLNA along with prostate volume had superior performance over PSA in identifying patients with prostate cancer (Kiebish et al Scientific Reports, 2021 Jul 23, 11(1)). Herein, we refined our analysis and establish FLNA alone as a serum biomarker for stratifying men with BPH vs prostate cancer as well as those with high Gleason prostate cancers compared to the current diagnostic paradigm of using PSA. This simplified approach demonstrates clinical actionability as a test with utility in AA and CA men and represents a significant opportunity to decrease the need for unnecessary biopsies for prostate cancer diagnosis. A clinical test is being developed to address this important medical need. Citation Format: Nischal Mahaveer Chand, Poornima K. Tekumalla, Albert Dobi, Amina Ali, Gregory M. Miller, Juan J. Aristizabal-Henao, Elder Granger, Stephen J. Freedland, Shiv Srivastava, Jose Arturo Rodriguez Rivera, Arturo Mendoza, David G. McLeod, Niven R. Narain, Michael A. Kiebish. Serum Filamin A is a prognostic biomarker for screening benign prostatic hyperplasia vs prostate cancer in Caucasian and African American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2196.