Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 May 8;29(1):272.
doi: 10.1186/s40001-024-01869-6.

Human pan-cancer analysis of the predictive biomarker for the CDKN3

Yingjun Chen #  1 , Dai Li #  2 , Kaihui Sha  3 , Xuezhong Zhang  4 , Tonggang Liu  5
Affiliations

Human pan-cancer analysis of the predictive biomarker for the CDKN3

Yingjun Chen et al. Eur J Med Res. .

Abstract

Background: Cell cycle protein-dependent kinase inhibitor protein 3 (CDKN3), as a member of the protein kinase family, has been demonstrated to exhibit oncogenic properties in several tumors. However, there are no pan-carcinogenic analyses for CDKN3.

Methods: Using bioinformatics tools such as The Cancer Genome Atlas (TCGA) and the UCSC Xena database, a comprehensive pan-cancer analysis of CDKN3 was conducted. The inverstigation encompassed the examination of CDKN3 function actoss 33 different kinds of tumors, as well as the exploration of gene expressions, survival prognosis status, clinical significance, DNA methylation, immune infiltration, and associated signal pathways.

Results: CDKN3 was significantly upregulated in most of tumors and correlated with overall survival (OS) of patients. Methylation levels of CDKN3 differed significantly between tumors and normal tissues. In addition, infiltration of CD4 + T cells, cancer-associated fibroblasts, macrophages, and endothelial cells were associated with CDKN3 expression in various tumors. Mechanistically, CDKN3 was associated with P53, PI3K-AKT, cell cycle checkpoints, mitotic spindle checkpoint, and chromosome maintenance.

Conclusion: Our pan-cancer analysis conducted in the study provides a comprehensive understanding of the involvement of CDKN3 gene in tumorigenesis. The findings suggest that targeting CDKN3 may potentially lead to novel therapeutic strategies for the treatment of tumors.

PubMed Disclaimer

Conflict of interest statement

All the authors declare no conficts of interest.

Figures

Fig. 1
Fig. 1
CDKN3 mRNA expression in pan-cancers. A CDKN3 mRNA expression in 33 tumors from TCGA-GTEx samples. B CDKN3 mRNA expression in 33 tumors from the TCGA database. C CDKN3 expression was observed in 23 paired tumor specimens from the TCGA database. (ns, p ≥ 0.05; *p < 0.05; **p < 0.01;***p < 0.001)
Fig. 2
Fig. 2
CDKN3 expression correlates with OS, DSS, and PFIin pan-cancer survival analysis. A Forest plots of the OS survival results. B Forest plots of the DSS survival results. C Forest plots of the PFI survival results
Fig. 3
Fig. 3
Clinical metrics and CDKN3 expression's relationship A–D CDKN3 expression was related to gender. E–H Expression of CDKN3 was related to the T stage. I–N CDKN3 expression was related to the N stage. O–T CDKN3 expression was related to pathologic stage. (*p < 0.05; **p < 0.01; ***p < 0.001)
Fig. 4
Fig. 4
The CDKN3 prognostic signature was combined with independent TCGA components to create our hybrid nomogram. A Creation of a nomogram model that takes CDKN3 expression in KIRC into account. B Using calibration curves for 1, 3, and 5 years, we assessed the KIRC nomogram model's prediction accuracy. C The expression of CDKN3 in LIHC is modelled using a nomogram. D Using calibration curves for 1, 3, and 5 years, we assessed the LIHC nomogram model's prediction accuracy
Fig. 5
Fig. 5
Analysis of the relationship between CDKN3 expression and immune infiltration of CD4 + T cells (A), Cancer associated fibroblasts (B), endothelial cells (C), and Macrophages (D)
Fig. 6
Fig. 6
The methylation level of CDKN3 in ESCA, KIRC, HNSC, LUSC, TGCT, and PAAD
Fig. 7
Fig. 7
Analysis of CDKN3-related genes' functional enrichment. A Analyses of GO functional enrichment (BP, CC, and MF). B Analysis of KEGG pathways for 100 CDKN3-related genes
Fig. 8
Fig. 8
CDKN3-related genes' GSEA analysis. A–Q GSEA based on differential expression analyses for ACC, BLCA, HNSC, DLBC, LGG, KIRC, KIRP, LIHC, LUAD, LUSC, MESO, PAAD, UCEC, PRAD, STAD, TGCT and UVM
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Seferbekova Z, Lomakin A, Yates LR, Gerstung M. Spatial biology of cancer evolution. Nat Rev Genet. 2023;24:295–313. doi: 10.1038/s41576-022-00553-x. - DOI - PubMed
    1. Del Giudice M, et al. FOXA1 regulates alternative splicing in prostate cancer. Cell Rep. 2022;40(13):111404. doi: 10.1016/j.celrep.2022.111404. - DOI - PMC - PubMed
    1. Weeden CE, Hill W, Lim EL, Grönroos E, Swanton C. Impact of risk factors on early cancer evolution. Cell. 2023;186:1541–1563. doi: 10.1016/j.cell.2023.03.013. - DOI - PubMed
    1. Wang L, Sun L, Huang J, Jiang M. Cyclin-dependent kinase inhibitor 3 (CDKN3) novel cell cycle computational network between human non-malignancy associated hepatitis/cirrhosis and hepatocellular carcinoma (HCC) transformation. Cell Prolif. 2011;44:291–299. doi: 10.1111/j.1365-2184.2011.00752.x. - DOI - PMC - PubMed
    1. Gyuris J, Golemis E, Chertkov H, Brent R. Cdi1, a human G1 and S phase protein phosphatase that associates with Cdk2. Cell. 1993;75:791–803. doi: 10.1016/0092-8674(93)90498-f. - DOI - PubMed

MeSH terms

Substances

-