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

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

doi:10.3389/fmolb.2021.653805

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

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

Authors

Huan Deng^{1

2

3

4}, Qingqing Hang⁵, Dijian Shen^{1

2

3}, Hangjie Ying^{1

2

3}, Yibi Zhang⁶, Xu Qian^{1

2

3}, Ming Chen^{1

2

3}

Affiliations

¹ Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, China.
² Institute of Cancer Research and Basic Medical (IBMC), Chinese Academy of Sciences, Hangzhou, China.
³ Department of Radiation Oncology, Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.
⁴ College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
⁵ The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
⁶ Jiangxi Medical College, Nanchang University, Nanchang, China.

Abstract

Purpose: 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. Methods: 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. Results: 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. Conclusion: Our study suggests and validates that CDK1 and CDC20 are potential therapeutic targets and prognostic biomarkers of LUSC.

Keywords: experimental validation; gene set enrichment analysis; lung squamous cell carcinoma; protein-protein interaction network; survival analysis.