Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges to the identification of aggressive cancers remain unmet. Prostate cancer screening is driven by the prostate-specific antigen (PSA); however, in men with benign prostatic hyperplasia (BPH) due to an enlarged prostate and elevated PSA, PSA's screening utility is diminished, resulting in many unnecessary biopsies. To address this issue, we previously identified a cleaved fragment of Filamin A (FLNA) protein (as measured with IP-MRM mass spectrometry assessment as a prognostic biomarker for stratifying BPH from prostate cancer and subsequently evaluated its expanded utility in Caucasian (CA) and African American (AA) men. All men had a negative digital rectal examination (DRE) and PSA between 4 and 10 ng/mL and underwent prostate biopsy. In AA men, FLNA serum levels exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.71 AUC and 12.2 OR in 48 men with BPH and 60 men with PCa) and outperformed PSA (0.50 AUC, 2.2 OR). In CA men, FLNA serum levels also exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.74 AUC and 19.4 OR in 191 men with BPH and 109 men with PCa) and outperformed PSA (0.46 AUC, 0.32 OR). Herein, we established FLNA alone as a serum biomarker for stratifying men with BPH vs. those with high Gleason (7-10) prostate cancers compared to the current diagnostic paradigm of using PSA. This approach demonstrates clinical actionability of FLNA alone without the requirement of prostate volume measurement as a test with utility in AA and CA men and represents a significant opportunity to decrease the number of unnecessary biopsies in aggressive prostate cancer diagnoses.
Cancers. 2024 Feb 08*** epublish ***
Nischal Mahaveer Chand, Poornima K Tekumalla, Matt T Rosenberg, Albert Dobi, Amina Ali, Gregory M Miller, Juan J Aristizabal-Henao, Elder Granger, Stephen J Freedland, Mark D Kellogg, Shiv Srivastava, David G McLeod, Niven R Narain, Michael A Kiebish
BPGbio Inc., Framingham, MA 01701, USA., Mid Michigan Health Centers, Jackson, MI 49201, USA., Center for Prostate Disease Research, John P. Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences and the Walter Reed National Military Medical Center, Bethesda, MD 20817, USA., Center for Integrated Research in Cancer and Lifestyle, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA., Department of Laboratory Medicine, Boston Children's Hospital Department of Pathology, Harvard Medical School, Boston, MA 02115, USA., Department of Biochemistry and Molecular & Cell Biology, Georgetown University School of Medicine, Washington, DC 20057, USA.