GMPPB (GDP-Mannose Pyrophosphorylase B)

Critically, PARP1 inhibition rescues GBP6 loss by suppressing TP63 and prevents ESCC progression. Overall, this study provides a systematic proteomic atlas of ESCC progression, identifies MOD as a pivotal clinical decision point, and proposes PARP1-TP63-GBP6 axis targeting as a novel intervention strategy.

By leveraging brain proteomic and transcriptomic data alongside large-scale GBM GWAS, we identified eight candidate genes and prioritized three-EGFR, SCFD1, and GMPPB-as high-confidence therapeutic targets. Notably, SCFD1 and GMPPB represent novel candidates. These findings advance our understanding of the molecular mechanisms underlying GBM and warrant further functional validation.

Our findings suggest that GMPPB, COMT, NME1, and GPX1 are potential risk genes for CWP, offering new insights into the molecular mechanisms underlying the condition. These genes represent promising targets for future research and therapeutic intervention development.

Our integrative approach reveals that causal gene expression profiles differ markedly between bulk-tissue and specific brain cell types, emphasizing cellular heterogeneity in MDD pathogenesis and informing precision therapeutic strategies. These findings underscore the necessity of considering cell type-specific gene regulation when developing therapeutic interventions for MDD.

PERSPECTIVE: The current post-GWAS analyses identified 18 high-confidence causal genes regulating chronic pain risk via cis-modulation of brain protein abundance, suggesting promising avenues for future chronic pain therapies. Additionally, the significant expression of these genes in the DRG indicated a potential contributory role, warranting further investigation.

Finally, we identify that the Hippo/MMP3 axis is essential for GMPPB-promoted GBM aggressiveness. These findings indicate that GMPPB represents a potential novel target for GBM treatment.