Genetic Distinctiveness in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma Cancer: Identifying Key Genomic Signatures through Differentially Expressed Gene Analysis.

Background: Lung cancer is the most commonly diagnosed cancer type and the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) accounts for more than 80% of all lung cancer cases and includes two main subtypes: lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Understanding the differences in genes causing the proliferation of LUAD and LUSC is key to advancing the diagnosis and targeted treatment development.

Aims: The aim of this study was to identify candidate genes and potential tumorigenesis mechanisms distinguishing LUAD and LUSC.

Methods: Three pooled transcriptomic datasets (GSE10245, GSE37745, and GSE43580) were analyzed from the Gene Expression Omnibus (GEO) database, with each dataset statistically tested for differentially expressed genes (DEGs). DEGs between lung LUAD and LUSC of the three datasets were analyzed with Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction (PPI) network was constructed to screen candidate genes.

Results: This study identified 138 shared DEGs among three patient-level gene expression datasets, containing 39 upregulated genes and 99 downregulated genes. The GO and KEGG enrichment analysis results showed the functions of DEGs to be mainly associated with epidermis development, cornified envelope, structural constituent of epidermis, and estrogen signaling pathway. Finally, through the PPI network, eight core genes were identified, including KRT14, KRT5, KRT6A, KRT16, SPRR1A, SPRR1B, SPRR3, and KRT6B.

Conclusion: We have elucidated key genes and molecular mechanisms linked to NSCLC subtypes. These findings have the potential to facilitate improved diagnostic and therapeutic targets for LUAD and LUSC biomarkers.