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.
前列腺癌对老年男性构成重大健康风险，其中侵袭性癌症的诊断识别仍面临挑战。目前前列腺癌筛查主要依赖前列腺特异性抗原（PSA），但对于因前列腺肥大导致良性前列腺增生（BPH）且PSA升高的男性，PSA的筛查效用会降低，导致许多不必要的活检。为解决这一问题，我们先前发现丝切蛋白A（FLNA）的裂解片段（通过IP-MRM质谱评估）可作为区分BPH与前列腺癌的预后生物标志物，并进一步评估了其在白种人（CA）和非裔美国人（AA）男性中的扩展应用价值。所有研究对象均经直肠指检（DRE）阴性且PSA值介于4-10 ng/mL之间，并接受了前列腺活检。在AA男性中，FLNA血清水平对区分BPH与侵袭性前列腺癌患者具有诊断价值（48例BPH与60例PCa患者中AUC为0.71，OR为12.2），其表现优于PSA（AUC 0.50，OR 2.2）。在CA男性中，FLNA血清水平同样对区分BPH与侵袭性前列腺癌患者具有诊断价值（191例BPH与109例PCa患者中AUC为0.74，OR为19.4），且显著优于PSA（AUC 0.46，OR 0.32）。本研究确立了FLNA作为单一血清生物标志物，在区分BPH与高格里森评分（7-10分）前列腺癌方面，相较于当前使用PSA的诊断模式具有优势。该方法证明了FLNA单独使用的临床可行性，无需进行前列腺体积测量，适用于AA和CA男性群体，并为减少侵袭性前列腺癌诊断中不必要的活检数量提供了重要机遇。
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