CDKN2A 高表达与结直肠癌不良预后相关，可能指导 PD-1 介导的免疫治疗。
High expression of CDKN2A is associated with poor prognosis in colorectal cancer and may guide PD-1-mediated immunotherapy.
机构信息
Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People's Republic of China.
出版信息
BMC Cancer. 2023 Nov 11;23(1):1097. doi: 10.1186/s12885-023-11603-w.
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.
背景
结直肠癌（CRC）是全球最常见的恶性肿瘤之一。针对程序性死亡蛋白 1（PD-1）及其配体（PD-L1）的免疫疗法是许多癌症的一种有前途的治疗选择，但在 CRC 中的治疗效果不佳。本研究旨在鉴定和验证免疫相关基因和 PD-1 相关基因对 CRC 免疫治疗的预后价值。
方法
对预后免疫相关 DEGs 和 PD-1 相关基因进行广泛分析，突出 CDKN2A 作为一个重要的重叠基因。为了进一步探讨其在 CRC 中的表达及其预后价值，我们进行了 qRT-PCR、Western blot 实验，并查阅了各种数据库。随后，我们进行了基因表达分析、生存和预后分析、富集分析、免疫浸润评估和 TIDE 分析，以评估 CDKN2A 的意义。
结果
在 CRC 中，与正常组织相比，CDKN2A 表达较高。发现 CDKN2A 的表达与炎症和肿瘤分期等临床病理特征有关。此外，CDKN2A 与免疫浸润之间存在显著相关性，具体涉及 CD4 T 细胞、CD8 T 细胞和巨噬细胞。对 CDKN2A 高表达的 CRC 样本的 GSEA 分析确定了 MYC 靶标-v2 和代谢途径相关基因的富集。此外，发现 UBE2I、CDK4、CDK6、TP53 和 CCND1 与 CDKN2A 显著共表达，提示这些基因在 CRC 和免疫治疗中可能发挥作用。
结论
我们的研究表明，CRC 中 CDKN2A 的高表达是一个有潜在价值的预后生物标志物，可能指导 PD-1 介导的免疫治疗。
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