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

recurrence or metastatic disease. Therefore, exploring following parameters were used: p<0.05, fold change >2,
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effective biomarkers for KIRC diagnosis and prognosis is and genes ranked within the top 10%. Using the messenger
urgently needed. ribonucleic acid (mRNA) expression from The Cancer
Genome Atlas (TCGA, https://portal.gdc.cancer.gov/),
Cancer development entails the gradual transformation
of normal cells into malignant ones, stemming from cancer versus normal data were analyzed. For statistically
significant data, the following information was collected:
abnormal responses to stimuli. This process is regulated cancer types, genes, dataset reference, sample sizes, fold
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at multiple levels – including transcription, translation, changes, t-test results, and p-values.
and post-translational modifications – that are essential
in maintaining cellular homeostasis. The ubiquitin- 2.2. UALCAN data analysis
6,7
proteasome system (UPS) facilitates rapid degradation of UALCAN (http://ualcan.path.uab.edu/analysis.html) is
transient proteins and plays an indispensable role in diverse a robust web-based tool. It specializes in processing data
biological processes, including genome stability and cell from two prominent resources: The MET500 cohort and
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cycle regulation. As a result, aberrant UPS function and TCGA, enabling in-depth genomic analysis. We analyzed
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regulation disrupt protein homeostasis, leading to a variety the relative expression of CUL1 – 3, CUL4A, CUL4B,
of illnesses, including cancer. 9 CUL5, CUL7, and CUL9 based on cancer stage across
In humans, the cullin family forms cullin-RING ligases various tumor subtypes. Student’s t-test was employed
(CRLs) with a RING protein during the ubiquitination to evaluate the disparity between the two groups, and
process. CRL dysfunction has been linked to kidney statistical significance was defined as p<0.05.
cancer in recent investigations. For instance, RCC has
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been associated with the dysfunction of CRLs containing 2.3. Gene expression profiling interactive analysis
CUL3. In the inherited condition known as Von Hippel- (GEPIA)
Lindau (VHL) disease, mutations in the CUL2-associated The GEPIA tool (http://gepia.cancer-pku.cn/) is an intuitive
substrate receptor VHL lead to the development of KIRC. web application integrating data from 8587 healthy and
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Furthermore, multiple investigations have found a link 9736 neoplastic samples from the TCGA and the Genotype-
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between CUL3 and Kelch-like ECH-associated protein 1 Tissue Expression initiatives. We made use of the KIRC
(Keap1) malfunction and papillary renal cell cancer. 12 dataset within the TCGA database to explore how cullin
family proteins were expressed in 523 patients. Patients
Consequently, we aimed to investigate the biological were categorized into low- and high-expression groups
roles and prognostic relevance of cullins in KIRC. In this based on individual gene transcript levels. The log-rank and
study, we identified the transcriptional patterns of cullin Mantel-Cox tests were utilized for statistical comparisons.
family members using ONCOMINE. We then performed
gene ontology (GO) functional and biological pathways In a separate cohort of 515 at-risk patients, we analyzed
analysis of cullins and their 20 related genes. Finally, we overall survival (OS) and disease-free survival (DFS). Where
examined their clinical characteristics and prognostic necessary, we calculated hazard ratios, 95% confidence
values in KIRC. Our findings reveal the potential biological intervals, and p-values to assess statistical significance.
function and prognostic value of cullins, which may aid 2.4. GeneMANIA data analysis
future diagnostic and therapeutic approaches for KIRC.
GeneMANIA (http://www.genemania.org) serves as an
2. Materials and methods online resource for comprehensive analysis of genetic

2.1. ONCOMINE data analysis and protein interactions, domain-protein similarities,
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co-localization, and biological pathways. This tool was
Designed specifically for translational research, the used to examine the link between cullins and their related
ONCOMINE platform (http://oncomine.org) offers a genes in the current investigation.
vast suite of bioinformatics tools. These resources enable
in-depth interrogation of gene expression profiles across 2.5. Metascape analysis
the entire genome, empowering researchers to derive Metascape (http://metascape.org) represents a software
meaningful insights from complex genomic data. Using application designed for annotating genes and conducting
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the “gene overview” and “dataset exploration” functions, enrichment analysis. In this research, we used Metascape
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transcriptional profiles of cullin family members (CUL1, to explore the roles of cullin family proteins and their
CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7, and CUL9) coexpressed genes. A significance threshold of p=0.01 was
across multiple malignancies were retrieved. Statistical established, with enrichment factors >1.5 and a minimum
significance was calculated through Student’s t-test. The count of 3 considered statistically significant.

Volume 4 Issue 3 (2025) 2 doi: 10.36922/GPD025070014