Characterization of Novel Progression Factors in Castration-Resistant Prostate Cancer Based on Global Comparative Proteome Analysis

SIMPLE SUMMARY: Here, we investigated prostate cancer (PCa) tissues at each stage of progression, from benign prostatic hyperplasia to castration-resistant prostate cancer (CRPC), based on quantitative proteomic technology, including tissues after androgen deprivation therapy (ADT). In total, we identified 4768 proteins, and 4069 of them were quantified. We performed a systematic bioinformatics analysis of 865 differentially expressed proteins (DEPs) in the combined PCa tissues. We found 15 DEPs, including FOXA1 and HMGN1–3, as novel factors were significantly involved in the progression to CRPC after ADT in T3G3. All targets were verified to have increased levels of FOXA1 and HMGN1–3 in CRPC by immunoblotting and indirect enzyme-linked immunosorbent assay. The FOXA1 and HMGN1–3 proteins could be used as CRPC-related factors in clinical therapeutic agents. ABSTRACT: Identifying the biological change from hormone-naïve prostate cancer to castration-resistant prostate cancer (CRPC) is a major clinical challenge for developing therapeutic agents. Although the pathways that lead to CRPC are not fully completely understood, recent evidence demonstrates that androgen signaling is often maintained through varied mechanisms. Androgen deprivation therapy (ADT) is used as a primary treatment for preventing the progression of prostate cancer (PCa). Here we investigated PCa tissues at each stage of progression, from benign prostatic hyperplasia (BPH) to CRPC, based on quantitative proteomic technology, including tissues after ADT. In total, 4768 proteins were identified in this study, of which 4069 were quantified in the combined PCa tissues. Among the quantified proteins, 865 were differentially expressed proteins (21.2%). Based on the quantitative protein results, we performed systematic bioinformatics analysis and found that the levels of 15 proteins, including FOXA1 and HMGN1–3, increased among T3G3, T3GX, and CRPC, despite the ADT. Among all targets, we verified the increased levels of FOXA1 and HMGN1–3 in CRPC by immunoblotting and indirect enzyme-linked immunosorbent assay. In summary, we discuss the changes in intracellular factors involved in the progression of CRPC PCa despite ADT. Moreover, we suggest that FOXA1 and HMGN1–3 proteins could be used as potential CRPC-related factors in clinical therapeutic agents.