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肺腺癌中CDK1的预后及免疫特征:一项系统分析

Prognostic and immunological characteristics of CDK1 in lung adenocarcinoma: A systematic analysis.

作者信息

Du Qingwu, Liu Wenting, Mei Ting, Wang Jingya, Qin Tingting, Huang Dingzhi

机构信息

Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

出版信息

Front Oncol. 2023 Mar 6;13:1128443. doi: 10.3389/fonc.2023.1128443. eCollection 2023.

Abstract

BACKGROUND

Cyclin-dependent kinases (CDKs) play a key role in cell proliferation in lung adenocarcinoma (LUAD). Comprehensive analysis of CDKs to elucidate their clinical significance and interactions with the tumor immune microenvironment is needed.

METHODS

RNA expression, somatic mutation, copy number variation, and single-cell RNA sequencing data were downloaded from public datasets. First, we comprehensively evaluated the expression profile and prognostic characteristics of 26 CDKs in LUAD, and CDK1 was selected as a candidate for further analysis. Then, a systematic analysis was performed to explore the relationships of CDK1 with clinical characteristics and tumor immune microenvironment factors in LUAD.

RESULTS

CDK1 was markedly upregulated at both the mRNA and protein level in LUAD. Moreover, overexpression of CDK1 was related to poor clinical outcomes. CDK1 coexpressed genes were mainly involved in the cell cycle, the DNA repair process, and the p53 signaling pathway. In addition, CDK1 expression was found to be correlated with the expression of multiple immunomodulators and chemokines, which participate in activating and suppressing the immune microenvironment. CDK1 expression was also correlated with increased infiltration of numerous immune cells, including CD4+ T cells and M1 macrophages. Patients with high CDK1 expression tended to have a poor response to immunotherapy but were sensitive to multiple chemotherapies and targeted drugs. The MDK-NCL and SPP1-CD44 ligand-receptor pairs were markedly activated in the intercellular communication network. CDK1 was an independent prognostic factor for LUAD and improved the ability to predict overall survival when combined with tumor stage.

CONCLUSION

CDK1 plays an essential role in reshaping the tumor immune microenvironment and might be a prognostic and treatment biomarker in LUAD.

摘要

背景

细胞周期蛋白依赖性激酶(CDKs)在肺腺癌(LUAD)的细胞增殖中起关键作用。需要对CDKs进行全面分析,以阐明其临床意义以及与肿瘤免疫微环境的相互作用。

方法

从公共数据集中下载RNA表达、体细胞突变、拷贝数变异和单细胞RNA测序数据。首先,我们全面评估了26种CDKs在LUAD中的表达谱和预后特征,并选择CDK1作为进一步分析的候选对象。然后,进行了系统分析,以探讨CDK1与LUAD临床特征和肿瘤免疫微环境因素之间的关系。

结果

CDK1在LUAD的mRNA和蛋白水平均显著上调。此外,CDK1的过表达与不良临床结局相关。CDK1共表达基因主要参与细胞周期、DNA修复过程和p53信号通路。此外,发现CDK1表达与多种免疫调节剂和趋化因子的表达相关,这些因子参与激活和抑制免疫微环境。CDK1表达还与包括CD4+T细胞和M1巨噬细胞在内的多种免疫细胞的浸润增加相关。CDK1高表达的患者对免疫治疗的反应往往较差,但对多种化疗和靶向药物敏感。MDK-NCL和SPP1-CD44配体-受体对在细胞间通讯网络中显著激活。CDK1是LUAD的独立预后因素,与肿瘤分期联合时可提高预测总生存的能力。

结论

CDK1在重塑肿瘤免疫微环境中起重要作用,可能是LUAD的预后和治疗生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31d6/10025485/9a1319262c1f/fonc-13-1128443-g001.jpg

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