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

CUL7 expression was reduced in multiple renal cancers in and CUL7 (p=0.023) correlated with extended OS.
the Jones et al. dataset: CCRCC (relative change = −2.639), Conversely, overexpression of CUL9 (p=0.0001) was linked
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renal pelvis urothelial carcinoma (relative change = −2.909); to a different survival trend. Moreover, for DFS in KIRC
chromophobe RCC (relative change = −2.489); papillary patients, elevated transcription levels of CUL1 (p=0.04),
RCC (relative change = −3.151). CUL9 expression was CUL4A (p=0.0002), and CUL5 (p=0.007) were significantly
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found to be enhanced in renal oncocytoma (relative associated with prolonged DFS.
change = 2.118) (Table 1).
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3.3. Co-expression and functional enrichment
3.2. Prognostic value of cullin family members in analysis of cullin family genes in KIRC patients
patients with KIRC
Leveraging GeneMANIA, we constructed an interaction
We employed UALCAN to investigate the connection network encompassing cullin family components and
between differential expression levels of cullin genes and their functionally associated genes, aiming to explore the
tumor grades in KIRC, aiming to find cullin members core biological functions of the cullin family in KIRC. The
involved in carcinogenesis, progression, and prognosis. analysis identified CACUL1, ANAPC2, ANAPC10, EXOC7,
The expression of CUL1, CUL2, CUL3, CUL4A, CUL4B, RP11-343C2.9, COG8, VPS51, HSF1, PRR5, ZZEF1, HSF2,
CUL5, CUL7, and CUL9 (p<0.001) was significantly HECTD3, EXOC8, HERC2, RNF217, ARIH1, ARIH2,
associated with tumor grade (Figure 2). The expression RNF144B, RNF19B, and RNF19A as key interactors,
levels of these genes demonstrated a strong correlation highlighting their roles in the regulatory functions of
with tumor progression, and survival curves stratified differentially expressed cullin genes (Figure 4).
by gene expression and tumor grade showed notable
differences in outcomes, suggesting that cullin proteins Subsequently, we employed Metascape to determine
may serve as potential prognostic biomarkers in KIRC. To how the cullin family genes and the 20 co-expressed genes
further explore these associations, we utilized the GEPIA mentioned above (Figure 5). The most significantly biological
database to explore the OS and DFS in KIRC prognosis processes included “ubiquitin-dependent protein catabolic
(Figure 3). For KIRC patients, elevated transcription of process,” “ubiquitin-mediated proteolysis,” “protein
CUL1 (p=0.0067), CUL2 (p=0.0012), CUL3 (p=0.0041), polyubiquitination,” “regulation of mitotic cell cycle,” “cell
CUL4A (p=0.0001), CUL4B (p=0.0031), CUL5 (p<0.0001), division,” “positive regulation of mitotic cell cycle,” and

Table 1. Differential expression of cullin genes between cancer and normal tissues in the ONCOMINE database
Gene Type of kidney cancer p‑value t‑statistic Fold change References
CUL1 Wilms tumor 0.008 3.267 2.172 Yusenko et al. 19
CUL2 Wilms tumor <0.001 5.268 2.617 Yusenko et al. 19
CUL3 Renal oncocytoma <0.001 −5.452 -4.876 Yusenko et al. 19
Chromophobe RCC 0.004 −4.014 -5.238 Yusenko et al. 19
CCRCC <0.001 −14.229 -2.340 Jones et al. 20
Renal pelvis urothelial carcinoma <0.001 −11.715 -2.133 Jones et al. 20
CUL4A Wilms tumor 0.002 4.499 4.757 Yusenko et al. 19
CUL4B Hereditary CCRCC <0.001 11.583 2.192 Beroukhim et al. 21
CUL5 Renal oncocytoma <0.001 −12.826 −3.055 Jones et al. 20
CCRCC <0.001 −14.018 −3.264 Jones et al. 20
Renal pelvis urothelial carcinoma <0.001 −7.377 −2.548 Jones et al. 20
Wilms tumor 0.006 −2.973 −2.094 Cutcliffe et al. 22
CUL7 CCRCC <0.001 −21.724 −2.639 Jones et al. 20
Renal pelvis urothelial carcinoma <0.001 −21.319 −2.909 Jones et al. 20
Chromophobe RCC <0.001 −20.148 −2.489 Jones et al. 20
Papillary RCC <0.001 −24.359 −3.151 Jones et al. 20
CUL9 Renal oncocytoma 0.001 5.157 2.118 Yusenko et al. 19
Abbreviations: CCRCC: Clear cell renal cell carcinoma; RCC: Renal cell carcinoma.

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