Lipid Metabolic Reprogramming During Progression to Castration-resistant Prostate Cancer Identified by Quantitative Proteomics.

Abstract

Background/aim: The progression of hormone-sensitive prostate cancer (HSPC) to castration-resistant prostate cancer (CRPC) as a result of resistance to androgen deprivation therapy (ADT) remains a major challenge in prostate cancer treatment.

Materials and methods: To explore the underlying mechanisms, we performed deep comparative proteomic profiling of HSPC and CRPC cell lines. LNCaP and C4-2 cell lines were cultured in isotopically labeled medium, combined, and digested, followed by liquid chromatography-mass spectrometry (LC-MS/MS) and bioinformatic analyses.

Results: Using SILAC-based proteomic analysis, 3,578 proteins were identified, with 2,474 quantified. In C4-2 cells, 41 proteins were significantly up-regulated, while 201 were down-regulated (fold-change >1.5 or <1.5-1, p<0.05). KEGG pathway analysis linked the increased proteins to fatty acid metabolism and biosynthesis of unsaturated fatty acids. Lipidomic analysis showed a significant rise in fatty acids like DHA, palmitic acid, stearic acid, and arachidic acid, aligning with the proteomic findings.

Conclusion: These results suggest that fatty acids play a key role in HSPC's progression to CRPC, possibly indicating that CRPC cells themselves may generate fatty acids.