简介 细胞周期蛋白依赖性激酶抑制剂 2A (CDKN2A) 是一种抑制性致癌基因，由于其在细胞周期调节和细胞分裂中的关键作用，该基因在乳腺癌、肝癌、甲状腺癌和胆管癌等多种类型的癌症中表达上调。尽管如此，它主要是在基因水平上进行研究，但作为生物标志物在泛癌分析方面的研究仍然很少，这项研究显示了其显着的潜在诊断和预后特征。然而，本研究旨在调查 CDKN2A 作为各种类型癌症的诊断和预后生物标志物的作用，主要关注结肠腺癌 (COAD)。方法我们通过使用各种生物信息学工具，包括肿瘤免疫估计资源（TIMER）2.0、基因表达谱交互分析（GEPIA）和大学，研究了不同类型癌症的泛癌分析中的 CDKN2A 基因表达，以显示其诊断潜在特征。阿拉巴马州伯明翰癌症数据分析门户 (UALCAN) 数据库。 TIMER 用于分析由从癌症基因组图谱 (TCGA) 获得的 10,000 个 RNA-seq 样本组成的 32 种癌症的基因表达，并分析肿瘤浸润免疫细胞。此外，GEPIA和UALCAN还进一步用于分析基因表达，包括基因调控、病理阶段和临床参数，包括性别、年龄和种族。因此，我们使用 GEPIA、UALCAN 和 Kaplan-Meier 绘图仪，特别是在腺癌中，通过研究其高表达与患者总体生存率的关联来研究 CDKN2A 的预后，以显示肿瘤进展。然后，我们利用cBio癌症基因组学门户网站（cBioPortal）研究了CDKN2A的基因改变，包括10项泛癌研究。我们通过使用基因表达综合库 (GEO) 中的公共队列来完成基因验证分析。结果 CDKN2A 在大多数癌症中呈上调趋势，在 5 种癌症中显着上调，这些癌症在三个数据库中通常可识别，包括乳腺浸润性癌 (p < 0.001)、肾嫌色细胞 (p < 0.001)、肾肾透明细胞癌(p < 0.001)、肾肾乳头状细胞癌 (p < 0.001) 和 COAD (p < 0.001)。 上调与 II 期和 III 期致病性 (pr(>F) = 0.00234) 的相关性显着不同，这在 COAD 中比在其他癌症中更明显。该基因在三种癌症中表现出与患者生存不良预后相关的高度上调，包括 COAD（对数秩 p = 0.011）、间皮瘤（对数秩 p = 5.9e-07）和肝癌（对数秩 p = 5.9e-07） p = 0.0045）。因此，COAD 是唯一经过全面分析、在 CDKN2A 高度上调期间显示出诊断和预后潜在特征的肿瘤。此外，CDKN2A 显示出深度缺失形式的罕见突变 (9%)，并显示随着免疫细胞浸润，与 CD4 T 细胞 (p = 0.0108)、巨噬细胞 (p = 0.0073) 和中性粒细胞 (p = 0.0272) 相关的上调COAD。  结论 我们的研究证明了 CDKN2A 的泛癌相关性，并揭示了 CDKN2A 的新颖性，强调了其作为 COAD 诊断预后生物标志物的潜力，因为 CDKN2A 主要在 COAD 的基因水平上进行研究。版权所有 © 2024，Salem 等人。

Introduction Cyclin-dependent kinase inhibitor 2A (CDKN2A) is a suppressor carcinogenic gene that is upregulated across various types of cancer including breast, liver, thyroid, and bile duct cancer due to its crucial role in cell cycle regulation and cell division. Nevertheless, it is mostly investigated at the genetic level, but it is still poorly studied on pan-cancer analysis as a biomarker and this study shows its significant potential diagnostic and prognostic characteristics. However, this study aims to investigate the role of CDKN2A as a diagnostic and prognostic biomarker across various types of cancer focusing primarily on colon adenocarcinoma (COAD). Methods We investigated CDKN2A gene expression in a pan-cancer analysis across different types of cancer to show its diagnostic potential characteristics by using various bioinformatic tools, including Tumor Immune Estimation Resource (TIMER) 2.0, Gene Expression Profiling Interactive Analysis (GEPIA), and University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) database. TIMER was used to profile gene expression across 32 types of cancer composed of 10,000 RNA-seq samples obtained from the Cancer Genome Atlas (TCGA) and to analyze the tumor-infiltrating immune cells. In addition, GEPIA and UALCAN were further used to analyze gene expression, in terms of gene regulation, pathological stages, and clinical parameters, including gender, age, and race. Therefore, we used GEPIA, UALCAN, and Kaplan-Meier plotter particularly across adenocarcinoma to investigate CDKN2A prognosis by studying its high expression association with the patient's overall survival rate to show the tumor progression. Then, we looked into the genetic alteration of CDKN2A by using the cBio Cancer Genomics Portal (cBioPortal), including 10 pan-cancer studies. We concluded the analysis with gene validation by using a public cohort in Gene Expression Omnibus (GEO). Results CDKN2A showed a trend of upregulation in most cancers and it was significantly upregulated in five cancers, which were commonly identifiable in three databases, including breast invasive carcinoma (p < 0.001), kidney chromophobe (p < 0.001), kidney renal clear cell carcinoma (p < 0.001), kidney renal papillary cell carcinoma (p < 0.001), and COAD (p < 0.001). The upregulation was significantly different in association with pathogenic stages II and III (pr(>F) = 0.00234) which was identifiable significantly in COAD more than in other cancers. The gene showed a high upregulation in association with poor prognosis of patient survival in three cancers, including COAD (log-rank p = 0.011), mesothelioma (log-rank p = 5.9e-07), and liver hepatocellular carcinoma (log-rank p = 0.0045). Therefore, COAD was the only comprehensively analyzed tumor to show a diagnostic and prognostic potential characteristic during high upregulation of CDKN2A. Furthermore, CDKN2A displayed a rare mutation in the form of deep deletion (9%) and revealed an upregulation associated with CD4+ T cells (p = 0.0108), macrophage (p = 0.0073), and neutrophils (p = 0.0272) as immune cells infiltrating COAD.  Conclusion Our study demonstrates the pan-cancer relevance of CDKN2A and revealed a novelty in showing CDKN2A underscores its potential as a diagnostic prognostic biomarker in COAD since CDKN2A is mostly studied at a genetic level across COAD.Copyright © 2024, Salem et al.