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

tissues harboring HPV16, in contrast to those positive for levels in a variety of cancers and is associated with a poor
other high-risk genotypes. CUL4A and CUL4B, two CRL4 prognosis. Such alterations in expression can aid medical
proteins, have been reported to have increased expression professionals in identifying potential tumors in the early
or amplification in a wide range of cancers. 6,32,35-39 CUL7 stages of the disease. This, in turn, can enhance the efficacy
(also known as KIAA0076, p185, p193) is an oncogene of treatment and patient survival rates. Furthermore,
that enhances cell growth, migration, proliferation, and in KIRC, high expression of CUL1 – 3, CUL4A, CUL4B,
invasion in hepatocellular carcinoma. 40,41 By increasing CUL5, and CUL7 correlates with favorable OS, whereas
p27, p53, and p21 protein expression, CUL7 knockdown CUL9 is linked to poor prognosis. This differential
decreased lung cancer cell proliferation and increased prognostic value highlights the potential for personalized
survival. 41,42 The downregulation of CUL7 also enhanced treatment planning based on cullin expression profiles,
microtubule re-establishment and induced migratory allowing clinicians to adopt more aggressive therapies or
and invasive capabilities in breast cancer cell lines, such intensive monitoring for high-risk patients.
as MDAMB-231 and BT549. 43,44 CUL7, associated with Nevertheless, our research has certain limitations.
Rabl3, is implicated in adverse prognostic outcomes for First, all data were gathered and evaluated through online
hepatocellular carcinoma and in paclitaxel responsiveness sources; hence, more research involving in vitro tests and
in breast cancer cellular models. 32
clinical samples is needed to validate our findings. Second,
In our study, we conducted GO and KEGG enrichment the underlying mechanisms, molecular connections,
analyses to investigate the interplay between the and clinical applications of individual cullin family
cullin genes and their associated genes. The biological members in KIRC remain incompletely understood and
processes identified include ubiquitin-dependent protein warrant further investigation. Finally, as a retrospective
degradation, ubiquitin-mediated proteolysis, and protein investigation, prospective outcomes clinical validation is
polyubiquitination. In addition, the activation of the essential to confirm the observed associations.
APC/C complex between the G1/S phase and early Future research should focus on elucidating the
anaphase, Golgi vesicle trafficking, and mitotic nuclear molecular mechanisms through which cullin proteins
division were also enriched.
regulate tumor and immune-related processes in
The TME plays a pivotal role in tumorigenesis and KIRC. Integration of advanced genomic and proteomic
23
therapy response. Immune cells residing within TME techniques may offer deeper insights into their functional
can either promote or inhibit tumor growth, thereby roles. Furthermore, clinical trials are needed to validate
contributing to varied clinical outcomes. The profile cullins as reliable biomarkers and therapeutic targets.
45
of tumor-infiltrating immune cells is increasingly The development of small-molecule inhibitors or
acknowledged as a prognostic biomarker for customized immunomodulators specifically targeting cullin pathways
treatment selection and better patient management. may open new avenues for precision oncology.
46
Using the TIMER database, we found that cullin expression
is closely linked to the infiltration of six immune cell 5. Conclusion
+
types in KIRC: dendritic cells, B cells, CD4 T cells, The present study investigated the potential value of cullin
macrophages, neutrophils, and CD8 T cells. This suggests family members as diagnostic and prognostic biomarkers
+
that cullins may be associated with both immunological for KIRC through a systematic bioinformatic analysis.
status and disease prognosis. Our study aims to provide First, the mRNA expression patterns of cullin family
insights into the immune landscape of KIRC, facilitating members in renal cancer patients were analyzed using
the advancement of novel immunotherapeutic strategies. the ONCOMINE database. The results demonstrated
The immune response has been identified as a key aspect that CUL1, CUL2, CUL4A, CUL4B, and CUL9 exhibited
of carcinogenesis and treatment efficacy in KIRC. In view significant up-regulation in renal cancer tissues, whereas
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of the considerable morbidity and mortality associated CUL3, CUL5, and CUL7 demonstrated significant
with KIRC, identifying prognostic molecular markers that downregulation. Subsequently, the prognostic value of
alter immune response is essential for improving patient cullin family members in patients with KIRC was further
outcomes. evaluated, revealing that the genes may be involved in
In the context of cancer, alterations in the cullin the development of KIRC. To further investigate their
protein expression are of significant clinical significance. biological mechanisms, we constructed an interaction
As high expression of some cullin genes is associated with network comprising cullin family members and their
tumorigenesis and progression, they can serve as potential functionally associated genes using GeneMANIA,
diagnostic markers. For instance, CUL1 is expressed at high identifying 20 coexpressed genes in the process. Functional

Volume 4 Issue 3 (2025) 10 doi: 10.36922/GPD025070014