» Articles » PMID: 36699449

Prognostic Significance of CKAP2L Expression in Patients with Clear Cell Renal Cell Carcinoma

Overview
Journal Front Genet
Date 2023 Jan 26
PMID 36699449
Authors
Affiliations
Soon will be listed here.
Abstract

Cytoskeleton-associated protein 2-like protein (CKAP2L) is thought to promote the progression of glioma, breast cancer, and ovarian cancer. However, the role of cytoskeleton-associated protein 2-like protein in clear cell renal cell carcinoma (ccRCC) is still unclear. The study aimed to investigate the roles and mechanisms of cytoskeleton-associated protein 2-like protein in clear cell renal cell carcinoma. The level of cytoskeleton-associated protein 2-like protein in tumors was explored by using UALCAN and Oncomine databases. Gene expression datasets of clear cell renal cell carcinoma from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) were also used to validate the cytoskeleton-associated protein 2-like protein level in clear cell renal cell carcinoma. Survival analysis was performed to investigate the relationship between cytoskeleton-associated protein 2-like protein level and prognosis of clear cell renal cell carcinoma patients. Cox regression analysis was used for identifying the independent prognostic factors. Gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), protein-protein interaction analysis, co-expression analysis, and immune infiltration analysis were used to explore the potential mechanisms of cytoskeleton-associated protein 2-like protein in clear cell renal cell carcinoma. Moreover, the levels of cytoskeleton-associated protein 2-like protein in clinical clear cell renal cell carcinoma tissues were also measured using RT-PCR, immunohistochemical analysis, and Western blotting. M1 macrophages and CD4 T cells were also detected by immunohistochemistry between tumor and normal tissues. The level of cytoskeleton-associated protein 2-like protein was upregulated in clear cell renal cell carcinoma according to multiple databases and experimental verification. Upregulated cytoskeleton-associated protein 2-like protein is an independent prognostic factor, which might activate the JAK-STAT signaling pathway, the P53 signaling pathway, the TGF-β signaling pathway, the WNT signaling pathway, , in clear cell renal cell carcinoma. Protein-protein interaction analysis and co-expression analysis suggest that cytoskeleton-associated protein 2-like protein might interact with some proliferation proteins. Immune infiltration analysis indicates that cytoskeleton-associated protein 2-like protein may affect the level of activated CD4 memory T cells, M1 macrophages, CD8 T cells, and neutrophils in clear cell renal cell carcinoma. More M1 macrophage infiltrations in tumor tissues with higher cytoskeleton-associated protein 2-like protein were validated by clear cell renal cell carcinoma tumor tissues. Cytoskeleton-associated protein 2-like protein is upregulated in clear cell renal cell carcinoma tissues, which may promote progression of the disease. Cytoskeleton-associated protein 2-like protein is a potential target for prognostic markers and a potential treatment target in clear cell renal cell carcinoma.

Citing Articles

Human CKAP2L shows a cell cycle-dependent expression pattern and exhibits microtubule-stabilizing properties.

Kwon H, Joh J, Hong K FEBS Open Bio. 2024; 14(9):1526-1539.

PMID: 39073037 PMC: 11492392. DOI: 10.1002/2211-5463.13864.


Recent Advances in the Management of Clear Cell Renal Cell Carcinoma: Novel Biomarkers and Targeted Therapies.

Schiavoni V, Campagna R, Pozzi V, Cecati M, Milanese G, Sartini D Cancers (Basel). 2023; 15(12).

PMID: 37370817 PMC: 10296504. DOI: 10.3390/cancers15123207.

References
1.
Choueiri T, Bauer T, Papadopoulos K, Plimack E, Merchan J, Mcdermott D . Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med. 2021; 27(5):802-805. PMC: 9128828. DOI: 10.1038/s41591-021-01324-7. View

2.
Love M, Huber W, Anders S . Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014; 15(12):550. PMC: 4302049. DOI: 10.1186/s13059-014-0550-8. View

3.
Clark D, Dhanasekaran S, Petralia F, Pan J, Song X, Hu Y . Integrated Proteogenomic Characterization of Clear Cell Renal Cell Carcinoma. Cell. 2019; 179(4):964-983.e31. PMC: 7331093. DOI: 10.1016/j.cell.2019.10.007. View

4.
Ricketts C, Linehan W . Multi-regional Sequencing Elucidates the Evolution of Clear Cell Renal Cell Carcinoma. Cell. 2018; 173(3):540-542. DOI: 10.1016/j.cell.2018.03.077. View

5.
Karakaya T, Bilgic A, Eris D, Baser B, Mermer S, Yildiz O . Identification of a novel pathogenic variant in CKAP2L and literature review in a child with Filippi syndrome and congenital talipes equinovarus. Am J Med Genet A. 2021; 185(7):2198-2203. DOI: 10.1002/ajmg.a.62223. View