ZAKARI, Suleiman and Covenant University, Theses Masters (2024) ASSESSMENT OF SELECTED PLASMA PROTEIN LEVELS IN NIGERIAN PROSTATE CANCER PATIENTS AND IN-SILICO THERAPEUTIC TARGETING OF AR SIGNALING. Masters thesis, Covenant University.
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Abstract
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.
| Item Type: | Thesis (Masters) |
|---|---|
| Uncontrolled Keywords: | Androgen receptor, SPOP gene, SRC-3, Prostate Cancer, In-Silico, Therapeutic Targeting. |
| Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
| Divisions: | Faculty of Medicine, Health and Life Sciences > School of Medicine |
| Depositing User: | nwokealisi |
| Date Deposited: | 26 Sep 2024 07:59 |
| Last Modified: | 26 Sep 2024 07:59 |
| URI: | http://eprints.covenantuniversity.edu.ng/id/eprint/18461 |
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