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Updated: Jul 11, 2025
Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
High expression of CDKN2A is associated with poor prognosis in colorectal cancer and may guide PD-1-mediated
Yuying Dong1, Mingming Zheng1, Xiaoxuan Wang1
1Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
Background:
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Immunotherapy targeting the programmed death protein 1(PD-1) and its ligand (PD-L1), is a promising treatment option for many cancers, but has exhibited poor therapeutic efficacy in CRC. This study aimed to identify and validate the prognostic value of immune-related genes and PD-1-associated genes for immunotherapy treatment of CRC.
Methods:
An extensive analysis of prognostic immune-related DEGs and PD-1-related genes has highlighted CDKN2A as a vital overlapping gene. To further explore its expression in CRC and its prognostic value, we conducted qRT-PCR, Western blot experiments, and consulted various databases. Subsequently, we conducted gene expression analysis, survival and prognostic analysis, enrichment analysis, immune infiltration assessment, and TIDE analysis to assess the significance of CDKN2A.
Results:
In CRC, CDKN2A was highly expressed compared to normal tissue. It was found that CDKN2A expression was related to clinicopathological features such as inflammation and tumor stage. Furthermore, a significant correlation was identified between CDKN2A and immune infiltration, specifically involving CD4 T cells, CD8 T cells, and macrophages. The analysis of the GSEA of CRC samples with high CDKN2A expression identified enrichment of genes involved in MYC target-v2 and metabolism pathways. Furthermore, UBE2I, CDK4, CDK6, TP53, and CCND1 were found to be significantly coexpressed with CDKN2A, suggesting a potential role that these gene play in CRC and immunotherapy.
Conclusions:
Our study revealed that high CDKN2A expression in CRC is a potentially valuable prognostic biomarker, which may guide PD-1-mediated immunotherapy.
Insights
High CDKN2A expression in colorectal cancer (CRC) indicates a poor prognosis and may guide immunotherapy. This finding is crucial for predicting treatment response in CRC patients receiving immune checkpoint inhibitors.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Colorectal cancer (CRC) is a prevalent malignancy with limited immunotherapy efficacy.
- Programmed death protein 1 (PD-1) and its ligand (PD-L1) inhibitors show potential but are less effective in CRC.
- Identifying biomarkers is crucial for predicting immunotherapy response in CRC.
Purpose of the Study:
- To identify and validate immune-related and PD-1-associated genes for CRC immunotherapy.
- To investigate the prognostic value of CDKN2A in colorectal cancer.
Main Methods:
- Differential gene expression analysis and database consultation identified CDKN2A.
- Validated CDKN2A expression using qRT-PCR and Western blot.
- Performed survival, enrichment, immune infiltration, and TIDE analyses.
Main Results:
- CDKN2A was significantly upregulated in CRC tissues compared to normal tissues.
- High CDKN2A expression correlated with clinicopathological features and immune infiltration (CD4+, CD8+ T cells, macrophages).
- Enrichment analysis revealed MYC target-v2 and metabolism pathway involvement; co-expression with UBE2I, CDK4, CDK6, TP53, and CCND1 was observed.
Conclusions:
- Elevated CDKN2A expression serves as a potential prognostic biomarker in CRC.
- CDKN2A may guide the selection of patients for PD-1-mediated immunotherapy.
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