Abstract 4121: Correlation, interaction, and prognostic impact of SMC4 and NIPBL phosphorylation in endometrial carcinoma

Background: Uterine Corpus Endometrial Carcinoma (UCEC) poses treatment challenges due to limited options. Protein phosphorylation, a dynamic reversible process, emerges as optimal targets. Methods: We analyzed phosphoprotein, protein, and mRNA data of UCEC in the CPTAC dataset (PDC000126). Correlation network and hierarchical clustering were employed to identify core phosphoproteins and proteins. Protein-Protein Interaction network was constructed using the STRING database. Results:Data from 95 UCEC patients, mainly FIGO stage I, included 73,212 phosphoprotein sites (8,450 genes) and 9,099 protein expressions. Only genes expressed in ≥80% of samples were included. Generally, protein-mRNA expression correlation was high (median 0.51), while phosphoprotein-protein and mRNA correlations were weaker (median: 0). Using a correlation coefficient >0.4, we identified 259 phosphorylation sites that correlated with 91 proteins. Clustering identified 11 core phosphorylation sites that universally correlated with proteins and 15 core genes that universally correlated with phosphorylation sites. Further analysis found the phosphorylation sites that strongly associated with these core genes located at 72 genes. The interaction networks between the 14 core genes and 72 co-expressed genes revealed RFC4, TPX2, SMC4, and NCAPD2 as central nodes regulating at least 10 co-expressed genes. Survival analysis linked the 4 core genes to UCEC patient PFS and OS. By setting experimentally determined interactions >0.5, we identified previous confirmed phosphorylation counterparts of core genes: NCAPD2-NCAPG, RFC4-RFC1, SMC4-NCAPG, SMC4-NCAPD3, and SMC4-NIPBL. Notably, NIPBL harbored two phosphorylation sites (NIPBL_T599 and NIPBL_T592). Intriguingly, SMC4, NCAPG, and NCAPD3 are condensin complex subunits, while NIPBL is a cohesin-loading factor, suggesting coordinated regulation between the two protein complexes. Conclusion: The gene expression and protein phosphorylation network offer potential UCEC treatment targets. The SMC4-NIPBL interaction implies a harmonization between cohesin and condensin complexes, potentially impacting UCEC prognosis. Citation Format: Jie Zhang, Qin Yang, Feilong Zhao, Ding Zhang, Yantao Li. Correlation, interaction, and prognostic impact of SMC4 and NIPBL phosphorylation in endometrial carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4121.