G-Protein-Coupled Receptor-Associated Sorting Protein 1 Overexpression Is Involved in the Progression of Benign Prostatic Hyperplasia, Early-Stage Prostatic Malignant Diseases, and Prostate Cancer

Abstract

Background/Objectives: Prostate cancer (PCa) is a prevalent malignancy, necessitating accurate diagnostic methods to distinguish it from benign conditions such as benign prostatic hyperplasia (BPH). Current diagnostic tools, relying primarily on serum prostate-specific antigen (PSA) levels, lack specificity, leading to an over-diagnosis and unnecessary treatment of patients with benign conditions. This study explores G-protein-coupled receptor-associated sorting protein 1 (GASP-1) as a more sensitive biomarker for PCa detection. Methods: Prostate tissue microarrays of healthy, BPH, and prostate cancer patients with different Gleason scores were studied. Polyclonal antibodies targeted against GASP-1 were used for routine immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA) analyses. Results: The results indicated a 5-fold difference in serum GASP-1 levels between BPH and PCa, which was validated through GASP-1 IHC. Furthermore, a novel scoring system, the H-score, assesses GASP-1 granules' intensity and size, revealing a clear distinction between BPH and PCa. An additional analysis of GASP-1 expression between PCa cases with different Gleason scores reveals that GASP-1 overexpression correlates with PCa severity, providing insights into disease progression. Conclusions: The study supports GASP-1's role as a promising diagnostic marker, supplementing PSA testing, and offering improved risk stratification for PCa. Additionally, an open-source software system is introduced for an efficient GASP-1 granule color analysis, enhancing diagnostic accuracy.

Keywords: 2D HPLE; ELISA; GASP-1; benign prostatic hyperplasia; cancer diagnostic; cancer prevention; immunohistochemistry; prostate cancer biomarker.

Figure 1

GASP-1 ELISA for differentiating BPH from prostate cancer.

Figure 2

Overexpression of GASP-1 in BPH and different Gleason grades of prostate cancer. Staining score of GASP-1 expression was achieved by immunohistochemistry.

Figure 3

GASP-1 expression in normal and different BPH tissues. (A) Normal prostate tissue. (B) BPH case with low H-score (H = 20); (C,D) BPH cases with high H-score (H = 100). Scale bar = 100 µm. Green arrows in (D) point out mini glands.

Figure 4

GASP-1 expression in BPH and in prostate cancer. (A) BPH case with high H-score (H = 100); (B) prostate cancer with Gleason Score 3 + 3 (H = 120); (C) intraductal carcinoma of prostate (IDC-P) in lower right corner (H = 110), with adenocarcinoma in upper right corner; and (D) prostate cancer with Gleason Score 3 + 3 (H = 110). Scale bar = 100 µm.

Figure 5

Comparison between H&E (A) and GASP-1 IHC (B) in same prostate cancer tissue (Gleason Score 3 + 3). In (B), black arrows point out GASP-1 granules.

Figure 6

GASP-1 overexpression in different prostate cancer cases. (A) Gleason 3 + 3; (B) Gleason 4 + 4; (C) Gleason 4 + 5. Scale bar = 100 µm.

Figure 7

Analyses of GASP-1 expression in various stages of prostate cancer after color segregation. (A–C) are regular GASP-1 IHC while (D–F) show only GASP-1 expression without the interference of blue staining. (A,D) are for a BPH case; (B,E) are for a Gleason 3 + 4 case; and (C,F) are for a Gleason 4 + 5 case. Scale bar = 100 µm.