AccScience Publishing / GPD / Online First / DOI: 10.36922/GPD025070014
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ORIGINAL RESEARCH ARTICLE

Identification of cullin family members as novel diagnostic and prognostic biomarkers in kidney renal clear cell carcinoma

Shaohao Liu1,2 ,  Fei Wang1,2 ,  Yange Wang1,2 ,  Dandan Wang1,2 ,  Shaoping Ji1,2 ,  Na Fang1,2*
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1 Cell Signal Transduction Laboratory and Institute of Biomedical Informatics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Henan University, Kaifeng, China
2 Kaifeng Key Laboratory of Cell Signal Transduction, Kaifeng Science and Technology Bureau, Kaifeng, China
GPD, 025070014 https://doi.org/10.36922/GPD025070014
Received: 13 February 2025 | Revised: 15 May 2025 | Accepted: 20 May 2025 | Published online: 2 July 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Kidney renal clear cell carcinoma (KIRC) is a prevalent histological subtype of kidney cancer and one of the most invasive urinary tumors. Members of the cullin family play a pivotal role in driving the development and progression of neoplasms. Accumulating evidence suggests that cullins might play a significant part in the initiation and advancement of KIRC. In this study, the messenger ribonucleic acid expression profiles for eight members of the cullin family (CUL1 – 9) were noticeably upregulated in KIRC compared to normal tissue, whereas CUL3, CUL5, and CUL7 were downregulated. Moreover, our analysis demonstrated that higher expression levels of CUL1 – 3, CUL4A, CUL4B, CUL5, and CUL7 were significantly correlated with enhanced overall survival (OS) in KIRC patients. Co-expression gene analysis showed that the differential expression of cullins in KIRC was predominantly associated with 20 genes. Functional enrichment analysis indicated that cullins in KIRC primarily participated in ubiquitin-mediated protein degradation, facilitated protein polyubiquitylation, and regulated APC/C activators during the G1/S phase transition and early anaphase. Furthermore, cullin gene expression exhibited a positive correlation with the activity of tumor-infiltrating immune cells. These findings suggest that cullins may serve as diagnostic and prognostic biomarkers in KIRC patients.

Graphical abstract
Keywords
Kidney renal clear cell carcinoma
Cullin gene family
Bioinformatics analysis
Prognostic value
Funding
This work was supported by grants from the Henan Province Science and Technology Research Projects (Grant no.: 232102310208), Kaifeng City Science and Technology Research Projects (Grant no.: 2303009 and 2303011), and the Bioinformatics Center of Henan University (Grant no.: 2020YLXKJC02).
Conflict of interest
Shaoping Ji is an Associate Editor of this journal, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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