CDK1 是与泛癌症尤其是胃肠道肿瘤中免疫渗透相关的预后生物标志物

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jiemiao Shen, Xing Gong, Siyue Tan, Yuxin Zhang, Rong Xia, Shuyu Xu, Shaozhuo Wang, Haojie Zhou, Yinyue Jiang, Tie Zhao, Yi Zhang, Hua Tang, Chao Wang
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引用次数: 0

摘要

目的细胞周期蛋白依赖性激酶 1(CDK1)调节细胞周期,在大多数肿瘤中高度表达。CDK1 的表达与疾病的不良预后有关。本研究旨在确定 CDK1 在泛癌症中的预后价值,并探讨 CDK1 表达与免疫细胞浸润之间的关联:方法:利用在线数据库分析泛癌中 CDK1 的表达及其与预后的相关性。免疫浸润通过ESTIMATE和CIBERSORT算法进行评估。然后,我们评估了CDK1表达与肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)或肿瘤浸润免疫细胞之间的关系。此外,我们还进行了免疫相关基因的共表达分析和泛癌中 CDK1 表达的 GO 分析。最后,我们比较了 30 对临床胃肠道肿瘤样本中 CDK1 与免疫相关基因的表达谱:结果:我们的分析表明 CDK1 在大多数肿瘤组织中过表达,尤其是在胃肠道肿瘤中。在肾脏乳头状细胞癌(KIRP)、肝脏肝细胞癌(LIHC)、肺腺癌(LUAD)、胰腺腺癌(PAAD)、前列腺癌(PRAD)和肉瘤(SARC)中,CDK1的高表达与总生存期、疾病特异性生存期、无病间隔期和无进展间隔期差相关。此外,CDK1的表达与22种癌症类型中的TMB和8种癌症类型中的MSI显著相关,在子宫内膜癌(UCEC)中,MSI-高(MSI-H)状态和高肿瘤突变负荷(TMB-H)的频率更高、胃腺癌 (STAD)、肉瘤 (SARC)、直肠腺癌 (READ)、间皮瘤 (MESO)、头颈部鳞状细胞癌 (HNSC) 和结肠腺癌 (COAD) 中的频率更高。此外,CDK1的表达与免疫细胞浸润水平相关,如M0、M1或M2巨噬细胞、记忆CD4 T细胞、T滤泡辅助细胞和幼稚B细胞。我们的数据显示,CDK1 与多种癌症类型中的 47 个免疫相关基因和免疫检查点基因有显著相关性。此外,CDK1在胃肠道肿瘤样本中上调,尤其是在胃癌和肠癌中。胃癌中的 CDK1 与 IDO1 呈正相关,肠癌中的 CDK1 与 PD-1 呈正相关:综上所述,我们的数据证明了 CDK1 在泛癌症的肿瘤发生和转移中的作用。因此,CDK1 是一种潜在的预后生物标志物,也是肿瘤免疫治疗的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CDK1 Acts as a Prognostic Biomarker Associated with Immune Infiltration in Pan-Cancer, Especially in Gastrointestinal Tumors.

Objective: Cyclin-dependent kinase 1 (CDK1) regulates the cell cycle and is highly expressed in most tumors. CDK1 expression has been associated with poor disease prognosis. This study aimed to identify the prognostic value of CDK1 in pan-cancer and investigate the association between CDK1 expression and immune cell infiltration.

Methods: CDK1 expression and its correlation with prognosis in pan-cancer were analyzed using online databases. Immune infiltration was assessed by ESTIMATE and CIBERSORT algorithms. We then evaluated the relationship between CDK1 expression and tumor mutational burden (TMB), microsatellite instability (MSI), or tumor-infiltrating immune cells. In addition, we performed the co-expression analysis of immune-related genes and GO analysis with CDK1 expression in pan-cancer. Finally, we compared the CDK1 expression profile with the immune-related genes in 30 pairs of clinical gastrointestinal tumor samples.

Results: Our analysis demonstrated overexpression of CDK1 in most tumor tissues, especially in gastrointestinal tumors. The high expression of CDK1 was associated with poor overall survival, disease-specific survival, disease-free interval, and progression-free interval in kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), pancreatic adenocarcinoma (PAAD), prostate adenocarcinoma (PRAD), and sarcoma (SARC). Besides, CDK1 expression was significantly associated with TMB in 22 cancer types and MSI in 8 cancer types as well as greater frequencies of MSI-high (MSI-H) status and high tumor mutational burden (TMB-H) in uterine corpus endometrial carcinoma (UCEC), stomach adenocarcinoma (STAD), sarcoma (SARC), rectum adenocarcinoma (READ), mesothelioma (MESO), head and neck squamous cell carcinoma (HNSC), and colon adenocarcinoma (COAD). In addition, CDK1 expression correlated with immune cell infiltrating levels, such as M0, M1, or M2 macrophages, memory CD4 T cells, T follicular helper cells, and naive B cells. Our data showed that CDK1 was remarkably correlated with 47 immune-related and immune checkpoint genes in many cancer types. Furthermore, CDK1 was up-regulated in gastrointestinal tumor samples, especially in gastric cancer and intestinal cancer. CDK1 was positively correlated with IDO1 in gastric cancer and PD-1 in intestinal cancer.

Conclusion: Taken together, our data demonstrated the roles of CDK1 in oncogenesis and metastasis in pan-cancer. Thus, CDK1 is a potential prognostic biomarker and a target for tumor immunotherapy.

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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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