Proteogenomic Analysis of Prostatic Tissues: lmpact of Missense Mutations (IMAGE)
Caption
Missense mutations influence protein abundance in prostate cancer. Using a SILAC-based quantitative proteomics approach, we identified significant proteomic differences between healthy and tumor tissues, demonstrating that missense mutations correlate with changes in protein expression. Specifically, RefSeq Abundant proteins were linked to essential metabolic and structural processes, while Variant Abundant proteins were associated with pathways involved in apoptosis inhibition, immune modulation, and metabolic reprogramming.
Spearman’s correlation analysis revealed a significant negative correlation (p < 0.05) between protein intensity difference and protein intensity ratio, indicating that missense mutations contribute to alterations in protein abundance. Additionally, Oncodrive analysis identified ACTB and PPIF as mutation hotspots. ACTB mutations may affect cell adhesion and metastasis, while PPIF variants are linked to mitophagy regulation and tumor survival. PROVEAN classification further confirmed that specific mutations in PGK1, HSPA9, and MDH2 have deleterious effects on protein stability and function.
Unlike sequencing-based studies, which infer the effects of mutations, our proteogenomic approach directly validates their impact on protein expression, reinforcing their biological and clinical relevance. This methodology enabled the identification of novel mutations in PNP, CSRP1, and GEMIN6, suggesting potential roles in immune modulation, cytoskeletal organization, and metabolic adaptation. Furthermore, our findings highlight possible interactions between neutrophil-associated proteins and tumor immune evasion, warranting further investigation into their therapeutic potential.
Credit
Lucas Marques da Cunha
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License
CC BY-NC