Association of CDKN2A overexpression with poor prognosis, radioresistance, and immunosuppression in colorectal cancer
5 affiliations
- 1Department of Radiation Oncology, Fujian Medical University Union Hospital, Fujian Key Laboratory of Intelligent Imaging and Precision Radiotherapy for Tumors (Fujian Medical University), Clinical Research Center for Radiology and Radiotherapy of Fujian Province (Digestive, Hematological and Breast Malignancies) , , ,
- 2Department of Hematology, Fuzhou University Affiliated Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital , , ,
- 3Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital , , ,
- 4Fujian Children’s Hospital, Fujian Medical University , , ,
- 5Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University , , ,
Abstract
Background: In colorectal cancer (CRC), dysregulated cyclin-dependent kinase inhibitor 2A (CDKN2A) contributes to disease progression. This investigation sought to explore the link between CDKN2A expression and the effectiveness of radiotherapy in CRC, and to investigate the underlying mechanisms.
Methods: Transcriptomic and clinical datasets were procured from the Cancer Genome Atlas and Gene Expression Omnibus databases. Immune cell infiltration was assessed using xCell, CIBERSORT, and EPIC methods. Biological mechanisms were investigated through the utilization of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. HCT 116 cells were used for in vitro and in vivo experiments.
Results: Bulk and single-cell transcriptome analyses and immunohistochemistry consistently revealed elevated CDKN2A expression in tumor specimens from patients with CRC. Patients with tumors that were nonresponsive to neoadjuvant chemoradiotherapy had significantly higher CDKN2A expression than those of responders (P = 0.039). CDKN2A knockdown in tumor led to a marked decrease in the proliferation, invasion, and migration capabilities, and this effect was enhanced by combined X-ray irradiation. Elevated CDKN2A expression was linked to markedly worse survival. In the tumor immune microenvironment, CDKN2A expression was negatively linked to CD8+ cell infiltration and positively correlated with the levels of immunosuppressive factors. Functional enrichment analysis indicated that elevated CDKN2A expression is linked to transcriptional regulation, amino acid metabolism, protein folding, and the TGF-β signaling pathway.
Conclusion: In CRC, CDKN2A overexpression is associated with unfavorable responses to radiotherapy, an immunosuppressive tumor microenvironment, and poor prognosis. Suppression of CDKN2A expression could potentially improve therapeutic outcomes in CRC patients. More experimental and clinical studies are still needed to verify and further distinguish the similarities and differences between colon cancer and rectal cancer.
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BibTeX
@article{lin2026association,
title = {{Association of CDKN2A overexpression with poor prognosis, radioresistance, and immunosuppression in colorectal cancer}},
author = {Yaobin Lin and Zhihong Wang and Gaoda Ju and Yueying Zhang and Zongwei Huang and Shan Liu and Benhua Xu and Zhao Zhan},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1955910},
url = {https://europepmc.org/article/PMC/PMC13719471},
note = {CC BY},
}
RIS
TY - JOUR
TI - Association of CDKN2A overexpression with poor prognosis, radioresistance, and immunosuppression in colorectal cancer
AU - Yaobin Lin
AU - Zhihong Wang
AU - Gaoda Ju
AU - Yueying Zhang
AU - Zongwei Huang
AU - Shan Liu
AU - Benhua Xu
AU - Zhao Zhan
PY - 2026
DA - 2026/10/16
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1955910
UR - https://europepmc.org/article/PMC/PMC13719471
AB - Background: In colorectal cancer (CRC), dysregulated cyclin-dependent kinase inhibitor 2A (CDKN2A) contributes to disease progression. This investigation sought to explore the link between CDKN2A expression and the effectiveness of radiotherapy in CRC, and to investigate the underlying mechanisms. Methods: Transcriptomic and clinical datasets were procured from the Cancer Genome Atlas and Gene Expression Omnibus databases. Immune cell infiltration was assessed using xCell, CIBERSORT, and EPIC methods. Biological mechanisms were investigated through the utilization of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. HCT 116 cells were used for in vitro and in vivo experiments. Results: Bulk and single-cell transcriptome analyses and immunohistochemistry consistently revealed elevated CDKN2A expression in tumor specimens from patients with CRC. Patients with tumors that were nonresponsive to neoadjuvant chemoradiotherapy had significantly higher CDKN2A expression than those of responders (P = 0.039). CDKN2A knockdown in tumor led to a marked decrease in the proliferation, invasion, and migration capabilities, and this effect was enhanced by combined X-ray irradiation. Elevated CDKN2A expression was linked to markedly worse survival. In the tumor immune microenvironment, CDKN2A expression was negatively linked to CD8+ cell infiltration and positively correlated with the levels of immunosuppressive factors. Functional enrichment analysis indicated that elevated CDKN2A expression is linked to transcriptional regulation, amino acid metabolism, protein folding, and the TGF-β signaling pathway. Conclusion: In CRC, CDKN2A overexpression is associated with unfavorable responses to radiotherapy, an immunosuppressive tumor microenvironment, and poor prognosis. Suppression of CDKN2A expression could potentially improve therapeutic outcomes in CRC patients. More experimental and clinical studies are still needed to verify and further distinguish the similarities and differences between colon cancer and rectal cancer.
SN - 2296-634X
ER -