Differentially genes expressed were identified using iDEP tool. A total of 4513 DEGs were identified in LUAD and 5369 in LUSC. The upregulated and downregulated genes were applied to analyze the GO: biological process, cellular component, molecular function, and KEGG pathway of each type. The highly significant genes in both LUSC and LUAD were enriched in terms that linked with cell cycle and division, chromosome and chromosomal regions, and DNA repair and building. In LUSC the KEGG pathways enriched by the upregulated genes were basal cell carcinoma, mismatch repair, biosynthesis of cofactors, and pentose and glucuronate interconversions, while in LUAD, the KEGG pathways which focused on signaling pathways were enriched by downregulated genes and metabolic pathways which were enriched by upregulated genes. A protein-protein interaction network was constructed based on the STRING database, and the network was visualized and analyzed by Cytoscape app. From the protein-protein interaction network, hub genes were identified. A total of 9 genes in LUSC and 11 genes in LUAD were determined as candidate hub genes, 6 hub genes EGFR, CDK1, IL6, GAPDH, CCNB1, and CDH1 were common in both LUSC and LUAD. Validation of expression of candidate hub genes was applied based on the TCGA database using GEPIA tool, and the validation was identical to our results. The analysis of gene alteration, overall survival, and clinical parameters of hub genes was performed based on TCGA database using cBioPortal. In clinical parameters, the correlation between gene expression of hub genes and disease stages was examined, as no clear correlation was observed between variance in gene expression and the first three stages of the disease.
The results obtained in this study may help in understanding more about the molecular mechanisms and the functional pathways that intersect and differ between LUSC and LUAD, and this may enhance the opportunities for new strategies for prevention and treatment.
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