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

Figure 4. Gene-gene interaction network of CUL1 – 9 in KIRC (GeneMANIA). This network was constructed to elucidate the fundamental mechanisms
underlying cullin family gene functionality. The analysis uncovered numerous genes involved in the regulatory functions of differentially expressed cullin
family genes.
Abbreviation: KIRC: Kidney renal clear cell carcinoma.

cell types: (1) CUL1 expression was positively associated 4. Discussion
with B cells, CD8⁺ T cells, CD4⁺ T cells, macrophages, and In this study, the mRNA expression levels of CUL1, CUL2,
neutrophils. (2) CUL2 expression was positively correlated CUL4A, CUL4B, and CUL9 were found to be significantly
with B cells, CD8⁺ T cells, CD4⁺ T cells, macrophages, higher in kidney cancer tissues compared to normal tissues.
neutrophils, and dendritic cells. (3) CUL3 showed Furthermore, elevated expression levels of CUL1 – 3,
associations with infiltration by B cells, CD8⁺ T cells, CD4⁺ CUL4A, CUL4B, CUL5, and CUL7 were notably correlated
T cells, macrophages, neutrophils, and dendritic cells. with improved OS in patients with KIRC, whereas high
(4) CUL4A expression was positively linked to B cells, CUL9 expression was markedly associated with poorer OS
CD4⁺ T cells, macrophages, neutrophils, and dendritic outcomes. CRLs, composed of a RING protein and cullin
cells. (5) CUL4B showed positive correlations with B cells, protein, are involved in the degradation of several oncogenic
CD8⁺ T cells, CD4⁺ T cells, macrophages, neutrophils, and proteins and tumor suppressors, and their dysregulation
dendritic cells. (6) CUL5 expression was also associated is associated with increased tumor growth. There is
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with infiltration by B cells, CD8⁺ T cells, CD4⁺ T cells, significant evidence that CRL malfunction contributes to
macrophages, neutrophils, and dendritic cells. (7) CUL7 kidney tumorigenesis. KIRC is caused by mutations in
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and CUL9 exhibited significant associations with CD4⁺ T the CUL2 substrate receptor VHL in the inherited VHL
cells and neutrophils. syndrome. RCC has also been linked to CUL3-containing

Volume 4 Issue 3 (2025) 7 doi: 10.36922/GPD025070014