Page 70 - GPD-4-3

Gene & Protein in Disease

ORIGINAL RESEARCH ARTICLE
Identification of cullin family members as novel

diagnostic and prognostic biomarkers in kidney
renal clear cell carcinoma

Shaohao Liu 1,2 , Fei Wang , Yange Wang 1,2 , Dandan Wang 1,2 , Shaoping Ji 1,2 ,
1,2
and Na Fang *
1,2
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

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
*Corresponding author: expression profiles for eight members of the cullin family (CUL1 – 9) were noticeably
Na Fang upregulated in KIRC compared to normal tissue, whereas CUL3, CUL5, and CUL7 were
(fangna@henu.edu.cn) downregulated. Moreover, our analysis demonstrated that higher expression levels of
Citation: Liu S, Wang F, Wang Y, CUL1 – 3, CUL4A, CUL4B, CUL5, and CUL7 were significantly correlated with enhanced
Wang D, Ji S, Fang N. Identification overall survival (OS) in KIRC patients. Co-expression gene analysis showed that the
of cullin family members as differential expression of cullins in KIRC was predominantly associated with 20 genes.
novel diagnostic and prognostic
biomarkers in kidney renal clear cell Functional enrichment analysis indicated that cullins in KIRC primarily participated in
carcinoma. Gene Protein Dis. ubiquitin-mediated protein degradation, facilitated protein polyubiquitylation, and
2025;4(3):025070014. regulated APC/C activators during the G1/S phase transition and early anaphase.
doi: 10.36922/GPD025070014
Furthermore, cullin gene expression exhibited a positive correlation with the activity
Received: February 13, 2025 of tumor-infiltrating immune cells. These findings suggest that cullins may serve as
1st revised: May 4, 2025 diagnostic and prognostic biomarkers in KIRC patients.
2nd revised: May 15, 2025
Accepted: May 20, 2025 Keywords: Kidney renal clear cell carcinoma; Cullin gene family; Bioinformatics analysis;
Prognostic value
Published online: July 2, 2025
Copyright: © 2025 Author(s).
This is an Open-Access article
distributed under the terms of the 1. Introduction
Creative Commons Attribution
License, permitting distribution, Renal cell carcinoma (RCC) is the most fatal tumor in the urinary system, accounting for
and reproduction in any medium,
1
provided the original work is 2 – 3% of adult cancers and 90% of renal malignancies. Kidney renal clear cell carcinoma
properly cited. (KIRC), the most common histological subtype of RCC, accounts for approximately 80%
2
Publisher’s Note: AccScience of all RCC cases. Since it is not sensitive to chemotherapy or conventional radiotherapy,
Publishing remains neutral with and targeted therapies for metastatic RCC (mRCC) are costly, radical or partial
regard to jurisdictional claims in 3
published maps and institutional nephrectomy remains the primary treatment for KIRC. However, approximately 40%
affiliations. of patients diagnosed with KIRC and undergoing nephrectomy ultimately develop local

Volume 4 Issue 3 (2025) 1 doi: 10.36922/GPD025070014