CDK1 and CCNA2 play important roles in oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is a malignant tumor that occurs in oral cavity and is dominated by squamous cells. The relationship between CDK1, CCNA2, and OSCC is still unclear. The OSCC datasets GSE74530 and GSE85195 configuration files were downloaded from the Gene Expression Omnibus (GEO) database and were derived from platforms GPL570 and GPL6480. Differentially expressed genes (DEGs) were screened. The weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, construction and analysis of protein-protein interaction (PPI) network, Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEGs. A total of 1756 DEGs were identified. According to Gene Ontology (GO) analysis, they were predominantly enriched in processes related to organic acid catabolic metabolism, centromeric, and chromosomal region condensation, and oxidoreductase activity. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DEGs were mainly concentrated in metabolic pathways, P53 signaling pathway, and PPAR signaling pathway. Weighted gene co-expression network analysis was performed with a soft-thresholding power set at 9, leading to the identification of 6 core genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1). The gene expression heatmap revealed that core genes (CDK1, CCNA2) were highly expressed in OSCC samples. Comparative Toxicogenomics Database analysis demonstrated associations between the 6 genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) and oral tumors, precancerous lesions, inflammation, immune system disorders, and tongue tumors. The associated miRNAs for CDK1 gene were hsa-miR-203a-3p.2, while for CCNA2 gene, they were hsa-miR-6766-3p, hsa-miR-4782-3p, and hsa-miR-219a-5p. CDK1 and CCNA2 are highly expressed in OSCC. The higher the expression of CDK1 and CCNA2, the worse the prognosis.

Figure 1.

Differential gene analysis. A total of 1756 DEGs. DEGs = differentially expressed genes.

Figure 2.

(A–D) GOKEGG enrichment analysis of DEGs. (A) Biological process analysis. (B) Cellular component analysis. (C) Molecular function analysis. (D) KEGG enrichment analysis. (E–H) GSEA of DEGs. (E) Biological process analysis. (F) Cellular component analysis. (G) Molecular function analysis. (H) KEGG enrichment analysis. DEGs = differentially expressed genes, KEGG = Kyoto Encyclopedia of Genes and Genomes.

Figure 3.

Metascape enrichment analysis. (A) Bar graph of enriched terms across input gene lists, colored by P values. (B) Network of enriched terms: colored by cluster ID, where nodes that share the same cluster ID are typically close to each other. (C) colored by P value, where terms containing more genes tend to have a more significant P value.

Figure 4.

Protein–protein interaction network. MCODE components identified in the gene lists.

Figure 5.

WGCNA. (A) β = 9,0.86. β = 9, 3.44. (B, C) The hierarchical clustering tree of all genes was constructed, and 28 important modules were generated. (D) The heatmap of correlation between modules and phenotypes. WGCNA = weighted gene co-expression network analysis.

Figure 6.

(A) The scatter map of correlation between GS and MM of related hub genes. (B) The DEGs screened by WGCNA and DEGs was used to obtain Venn map. One hundred twenty intersection genes were obtained. DEGs = differentially expressed genes, GS = gene significance, MM = module membership, WGCNA = weighted gene co-expression network analysis.

Figure 7.

Construction and analysis of protein–protein interaction (PPI) networks. (A) PPI network of DEGs. (B) CLUSTER was used to identify the central gene. (C) MCC was used to identify the central gene. (D) MNC was used to identify the central gene. (E) Six core genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) were obtained by merging using Venn diagrams. DEGs = differentially expressed genes.

Figure 8.

(A) The heatmap depicting the expression levels of differentially expressed genes related to ferroptosis in the merged matrix of GSE74530 and GSE85195 datasets. (B) CTD analysis. Six genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) are associated with liver tumors, hepatocellular carcinoma, invasive tumors, and end-stage liver disease. CTD = Comparative Toxicogenomics Database.