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Gene & Protein in Disease                                        Cullin family members as biomarkers in KIRC























































            Figure 2. The impact of cullin expression levels on KIRC patient survival by tumor grade (UALCAN). The results demonstrated statistically significant
            associations for all eight cullin genes shown (p<0.001). These findings suggest that the expression of cullin family members may be involved in the
            oncogenesis and development of KIRC.
            Abbreviation: KIRC: Kidney renal clear cell carcinoma.

            “mGolgi vesicle transport” (Figure 5A). A network of these   3.4. Immune cell infiltration related to cullin
            enriched terms was constructed and visualized based on   expression in KIRC
            cluster and identifier (Figures 5B and C). Furthermore, a   The tumor microenvironment  (TME), comprising
            protein-protein interaction (PPI) network was generated   fluids, immune cells, stromal cells, extracellular matrix
            and analyzed using the molecular complex detection   components, and a variety of cytokines and chemokines,
            (MCODE) algorithm within Metascape (Figure  5D-F).   plays a crucial role in tumor growth and recurrence.
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            The results identified a prominent MCODE component   Using TIMER, we investigated the relationship between
            consisting of ubiquitin E3 ligase complex members (CSN1,   cullin family genes and immune cell infiltration in KIRC
            CSN8, HRT1, SKP1, SKP2, CUL1, CUL2, and CUL3).     (Figure  6).  The results revealed  that  CUL1  and CUL2
            These proteins were predominantly associated with key   mRNA expressions were adversely associated with
            biological processes, including proteasome-mediated,   tumor purity. Moreover, we observed significant positive
            ubiquitin-dependent protein catabolic processes and   associations between the expression of multiple cullin
            proteasomal protein degradation pathways.          family  members  and  the  infiltration  of  various  immune



            Volume 4 Issue 3 (2025)                         5                           doi: 10.36922/GPD025070014
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