ASSESSMENT OF SELECTED PLASMA PROTEIN LEVELS IN NIGERIAN PROSTATE CANCER PATIENTS AND IN-SILICO THERAPEUTIC TARGETING OF AR SIGNALING
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Description
Prostate cancer (PCa) is one of the most common male cancers and one of the main cancer-related
causes of mortality in men. In 2020, there were more than 1.4 million fresh instances of PCa
worldwide. Therefore, more new and efficient therapeutic targets and biomarkers are needed
urgently for better PCa management. This study aimed to quantify SPOP, AR, and SRC-3 proteins
in PCa patients and non-cancer controls, and screen the potential inhibitors toward mutated SPOP
and Androgen Receptor Variant 7 (AR-V7) computationally. A case-control study design was
used, selecting 40 PCa patients with histologically confirmed cases and 40 healthy controls.
Plasma levels of SPOP, AR, and SRC-3 were estimated by ELISA. Moreover, computational
analysis, with the use of simulations, was conducted to predict the physiochemical properties of
some selected compounds from Caesalpinia bonduc, drug-likeness, and binding affinity toward
mutant SPOP and AR-V7.The mean SPOP, AR, and SRC-3 levels did not differ significantly
between PCa and controls (p > 0.05). Pearson correlation analysis revealed a very strong positive
correlation between AR and SRC-3 levels (r = 0.9, p < 0.0001), SPOP and AR levels was
moderately high (r = 0.7, p < 0.0001), while the correlation between SPOP and SRC-3 was more
moderate (r = 0.6, p < 0.0001). Computational analyses identified 4 C. bonduc compounds; 4,4'-
dihydroxy-2'-methoxy-chalcone (2'-methoxyisoliquiritigenin), 7,4'-dihydroxy-3,11-
dehydrohomoisoflavanone, 5,7,3',4'-tetrahydroxy-flavone (Luteolin), 7,3',4'-tetrahydroxy-3-
methoxyflavone (quercetin-3-methyl ether) designated as COMP1, COMP2, COMP3 and COMP4
respectively, with favorable physicochemical properties and drug-likeness. Molecular docking
showed that COMP2 and COMP3 exhibited stronger binding affinities to mutant SPOP than
Enzalutamide. COMP2, COMP3, and COMP4 also showed stronger binding to AR-V7 than
Apalutamide. While SPOP, AR, and SRC-3 levels did not differ between PCa and controls,
correlation results suggest a meaningful interplay between SPOP, AR, and SRC-3 in the context
of prostate cancer. Larger cohort proteomic profiling studies should be conducted to validate this
study's findings and establish the clinical relevance of protein profiling in prostate cancer
management. Computational analyses identified C. bonduc compounds: COMP2, COMP3, and
COMP4 with promising therapeutic potential targeting mutant SPOP and AR-V7. For their clinical
utility to be established, more validation is necessary.
Keywords
QD Chemistry, QH301 Biology, R Medicine (General), RC0254 Neoplasms. Tumors. Oncology (including Cancer)