Filamin A Is a Prognostic Serum Biomarker for Differentiating Benign Prostatic Hyperplasia from Prostate Cancer in...

Area of Science:

• Biochemistry
• Oncology
• Clinical Diagnostics

Background:

• Prostate cancer screening relies on prostate-specific antigen (PSA), but its utility is limited in men with benign prostatic hyperplasia (BPH).
• Elevated PSA in BPH can lead to unnecessary prostate biopsies, highlighting a need for improved diagnostic markers.
• Aggressive prostate cancer detection remains a challenge, particularly in differentiating it from BPH.

Purpose of the Study:

• To evaluate the diagnostic utility of serum Filamin A (FLNA) fragment levels for differentiating BPH from aggressive prostate cancer.
• To compare the performance of FLNA as a biomarker against prostate-specific antigen (PSA) in Caucasian (CA) and African American (AA) men.
• To establish FLNA as a standalone biomarker for improved prostate cancer diagnosis, reducing the need for prostate volume measurement.

Main Methods:

• Serum samples were collected from men with PSA levels between 4 and 10 ng/mL and negative digital rectal examination (DRE).
• Filamin A (FLNA) protein fragment levels were measured using IP-MRM mass spectrometry.
• Statistical analysis, including Area Under the Curve (AUC) and Odds Ratio (OR), was used to assess diagnostic utility in stratifying BPH from prostate cancer (Gleason score 7-10).

Main Results:

• In African American men, FLNA demonstrated diagnostic utility (0.71 AUC, 12.2 OR) outperforming PSA (0.50 AUC, 2.2 OR) in differentiating BPH from aggressive prostate cancer.
• In Caucasian men, FLNA also showed significant diagnostic utility (0.74 AUC, 19.4 OR), surpassing PSA's performance (0.46 AUC, 0.32 OR).
• FLNA alone proved effective in stratifying men with BPH versus those with high-grade prostate cancer, irrespective of prostate volume.

Conclusions:

• Serum FLNA levels serve as a clinically actionable biomarker for distinguishing benign prostatic hyperplasia from aggressive prostate cancer.
• FLNA offers improved diagnostic accuracy compared to PSA, particularly in diverse populations (AA and CA men).
• This biomarker has the potential to significantly reduce the number of unnecessary prostate biopsies, improving patient outcomes and healthcare efficiency.