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肺鳞状细胞癌患者中CDK1和CDC20的高表达水平与较差的预后相关。

High Expression Levels of CDK1 and CDC20 in Patients With Lung Squamous Cell Carcinoma are Associated With Worse Prognosis.

作者信息

Deng Huan, Hang Qingqing, Shen Dijian, Ying Hangjie, Zhang Yibi, Qian Xu, Chen Ming

机构信息

Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.

Institute of Cancer Research and Basic Medical (IBMC), Chinese Academy of Sciences, Hangzhou, China.

出版信息

Front Mol Biosci. 2021 Jul 7;8:653805. doi: 10.3389/fmolb.2021.653805. eCollection 2021.

Abstract

Progress related to the early detection and molecular targeted therapy of lung squamous cell carcinoma (LUSC) remains limited. The goal of our study was to identify key candidate indicators of LUSC. Three microarray datasets (GSE33532, GSE30219 and GSE19188) were applied to find differentially expressed genes (DEGs). Functional enrichment analyses of DEGs were carried out, and their protein-protein interaction (PPI) network was established. Hub genes were chosen from the PPI network according to their degree scores. Then, overall survival (OS) analyses of hub genes were carried out using Kaplan-Meier plotter, and their GSEA analyses were performed. Public databases were used to verify the expression patterns of CDK1 and CDC20. Furthermore, basic experiments were performed to verify our findings. A total of 1,366 DEGs were identified, containing 669 downregulated and 697 upregulated DEGs. These DEGs were primarily enriched in cell cycle, chromosome centromeric region and nuclear division. Seventeen hub genes were selected from PPI network. Survival analyses demonstrated that CDK1 and CDC20 were closely associated with OS. GSEA analyses revealed that cell cycle, DNA replication, and mismatch repair were associated with CDK1 expression, while spliceosome, RNA degradation and cell cycle were correlated with CDC20 expression. Based on The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (THPA) databases, CDK1 and CDC20 were upregulated in LUSC at the mRNA and protein levels. Moreover, basic experiments also supported the obvious upregulation of CDK1 and CDC20 in LUSC. Our study suggests and validates that CDK1 and CDC20 are potential therapeutic targets and prognostic biomarkers of LUSC.

摘要

肺鳞状细胞癌(LUSC)在早期检测和分子靶向治疗方面的进展仍然有限。我们研究的目的是确定LUSC的关键候选指标。应用三个微阵列数据集(GSE33532、GSE30219和GSE19188)来寻找差异表达基因(DEG)。对DEG进行功能富集分析,并建立其蛋白质-蛋白质相互作用(PPI)网络。根据中心度得分从PPI网络中选择枢纽基因。然后,使用Kaplan-Meier绘图仪对枢纽基因进行总生存(OS)分析,并进行基因集富集分析(GSEA)。利用公共数据库验证细胞周期蛋白依赖性激酶1(CDK1)和细胞分裂周期蛋白20(CDC20)的表达模式。此外,进行基础实验以验证我们的发现。共鉴定出1366个DEG,其中669个下调,697个上调。这些DEG主要富集在细胞周期、染色体着丝粒区域和核分裂中。从PPI网络中选择了17个枢纽基因。生存分析表明,CDK1和CDC20与OS密切相关。GSEA分析显示,细胞周期、DNA复制和错配修复与CDK1表达相关,而剪接体、RNA降解和细胞周期与CDC20表达相关。基于癌症基因组图谱(TCGA)和人类蛋白质图谱(THPA)数据库,CDK1和CDC20在LUSC中的mRNA和蛋白质水平均上调。此外,基础实验也支持LUSC中CDK1和CDC20明显上调。我们的研究表明并验证了CDK1和CDC20是LUSC潜在的治疗靶点和预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/419d/8292837/78bf81ea500a/fmolb-08-653805-g001.jpg

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