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

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

doi:10.3389/fmolb.2021.653805

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.

Highlights

Lung cancer is one of the most common cancer types with high cancer-related mortality and is estimated to lead to 228,820 cancer cases and 135,720 deaths in 2020 (Siegel et al, 2020)
Survival analyses demonstrated that CDK1 and CDC20 were closely associated with overall survival (OS)
gene set enrichment analysis (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

Summary

Introduction

Lung cancer is one of the most common cancer types with high cancer-related mortality and is estimated to lead to 228,820 cancer cases and 135,720 deaths in 2020 (Siegel et al, 2020). Non-small cell lung cancer (NSCLC) accounts for 85% of total lung cancer cases, and lung adenocarcinoma (LUAD) is the first prevalent histological type of NSCLC followed by lung squamous cell carcinoma (LUSC). Accumulating evidence indicated that overexpression and mutation of the genes are associated with carcinogenesis, proliferation, and/or worse prognosis of LUSC, including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), MET proto-oncogene (MET), and epidermal growth factor receptor (EGFR) (Sands et al, 2020). Key biomarkers involved in the carcinogenesis and progression of LUSC need to be identified, and effective therapeutic measures need to be developed

Objectives

Methods

Results

Discussion

Conclusion