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Clinicopathological Significance of Cyclin-Dependent Kinase 2 (CDK2) in Ductal Carcinoma In Situ and Early-Stage Invasive Breast Cancers.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2024 May 06; Vol. 25 (9). Date of Electronic Publication: 2024 May 06. - Publication Year :
- 2024
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Abstract
- Cyclin-dependent kinase 2 (CDK2) is a key cell cycle regulator, with essential roles during G1/S transition. The clinicopathological significance of CDK2 in ductal carcinomas in situ (DCIS) and early-stage invasive breast cancers (BCs) remains largely unknown. Here, we evaluated CDK2's protein expression in 479 BC samples and 216 DCIS specimens. Analysis of CDK2 transcripts was completed in the METABRIC cohort ( n = 1980) and TCGA cohort ( n = 1090), respectively. A high nuclear CDK2 protein expression was significantly associated with aggressive phenotypes, including a high tumour grade, lymph vascular invasion, a poor Nottingham prognostic index (all p -values < 0.0001), and shorter survival ( p = 0.006), especially in luminal BC ( p = 0.009). In p53-mutant BC, high nuclear CDK2 remained linked with worse survival ( p = 0.01). In DCIS, high nuclear/low cytoplasmic co-expression showed significant association with a high tumour grade ( p = 0.043), triple-negative and HER2-enriched molecular subtypes ( p = 0.01), Comedo necrosis ( p = 0.024), negative ER status ( p = 0.004), negative PR status ( p < 0.0001), and a high proliferation index ( p < 0.0001). Tumours with high CDK2 transcripts were more likely to have higher expressions of genes involved in the cell cycle, homologous recombination, and p53 signaling. We provide compelling evidence that high CDK2 is a feature of aggressive breast cancers. The clinical evaluation of CDK2 inhibitors in early-stage BC patients will have a clinical impact.<br />Competing Interests: The authors declare no conflicts of interest.
- Subjects :
- Humans
Female
Prognosis
Middle Aged
Biomarkers, Tumor metabolism
Biomarkers, Tumor genetics
Neoplasm Staging
Carcinoma, Ductal, Breast pathology
Carcinoma, Ductal, Breast metabolism
Carcinoma, Ductal, Breast genetics
Carcinoma, Ductal, Breast mortality
Aged
Gene Expression Regulation, Neoplastic
Neoplasm Invasiveness
Tumor Suppressor Protein p53 metabolism
Tumor Suppressor Protein p53 genetics
Cyclin-Dependent Kinase 2 metabolism
Cyclin-Dependent Kinase 2 genetics
Breast Neoplasms pathology
Breast Neoplasms genetics
Breast Neoplasms metabolism
Breast Neoplasms mortality
Carcinoma, Intraductal, Noninfiltrating pathology
Carcinoma, Intraductal, Noninfiltrating genetics
Carcinoma, Intraductal, Noninfiltrating metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 25
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 38732271
- Full Text :
- https://doi.org/10.3390/ijms25095053