Song Teng, Li Shuping, Zhao Ke, Zou Dandan, Zhang Miao, Wang Huaqing
Department of Oncology, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin, 300121, China.
The Institute of Translational Medicine, Tianjin Union Medical Center, NanKai University, Tianjin, 300121, China.
BMC Pulm Med. 2025 Apr 14;25(1):179. doi: 10.1186/s12890-025-03631-y.
Recent research has increasingly highlighted the significance of various forms of cell death in contributing to tumor heterogeneity and modulating anti-tumor immunity. However, the potential implications of cuproptosis-related genes (CRGs) in lung adenocarcinoma (LUAD) remains poorly explored.
We conducted a comprehensive analysis of the expression profiles of 19 CRGs in LUAD based on The Cancer Genome Atlas (TCGA). Utilizing consensus clustering, we stratified the TCGA cohort into two distinct LUAD subtypes (Cluster 1 and Cluster 2). The expression of CDKN2A was further validated across multiple datasets, including TCGA, GEO, Cancer Cell Line Encyclopedia (CCLE), and the Human Protein Atlas (HPA). The prognostic value of the CDKN2A was evaluated through univariate, multivariate, and survival analyses. Gene set enrichment analysis (GSEA) was performed to elucidate the molecular mechanisms associated with the CDKN2A. Additionally, we assessed the levels of immune cell infiltration in LUAD using the CIBERSORT, ESTIMATE, and XCELL algorithms.
By systematically analyzing the genetic alterations of 19 CRGs in LUAD, we found 15 differentially expressed genes between LUAD and adjacent normal tissues. Subsequently, using the consensus clustering method, we classified LUAD patients into two molecular subtypes and cluster 2 had a poor prognosis. CDKN2A emerged as a key gene of interest, exhibiting elevated expression in LUAD and correlating with adverse patient outcomes. Moreover, immunoinfiltration analysis revealed differential levels of immune cell infiltration between the CDKN2A high and CDKN2A low expression groups.
Our findings indicate that CDKN2A may serve as an effective prognostic biomarker for LUAD and may offer valuable insights into potential immunotherapeutic strategies for these patients.
Not applicable.
近期研究越来越强调各种形式的细胞死亡在导致肿瘤异质性和调节抗肿瘤免疫方面的重要性。然而，铜死亡相关基因（CRGs）在肺腺癌（LUAD）中的潜在影响仍未得到充分探索。
我们基于癌症基因组图谱（TCGA）对LUAD中19个CRGs的表达谱进行了全面分析。利用一致性聚类，我们将TCGA队列分为两种不同的LUAD亚型（簇1和簇2）。CDKN2A的表达在多个数据集（包括TCGA、GEO、癌细胞系百科全书（CCLE）和人类蛋白质图谱（HPA））中进一步得到验证。通过单变量、多变量和生存分析评估CDKN2A的预后价值。进行基因集富集分析（GSEA）以阐明与CDKN2A相关的分子机制。此外，我们使用CIBERSORT、ESTIMATE和XCELL算法评估LUAD中免疫细胞浸润水平。
通过系统分析LUAD中19个CRGs的基因改变，我们发现LUAD与相邻正常组织之间有15个差异表达基因。随后，使用一致性聚类方法，我们将LUAD患者分为两种分子亚型，簇2预后较差。CDKN2A成为一个关键的关注基因，在LUAD中表达升高且与患者不良预后相关。此外，免疫浸润分析显示CDKN2A高表达组和CDKN2A低表达组之间免疫细胞浸润水平存在差异。
我们的研究结果表明，CDKN2A可能作为LUAD的有效预后生物标志物，并可能为这些患者的潜在免疫治疗策略提供有价值的见解。
不适用。
