Transcriptomic analysis of + non-small cell lung cancer reveals an upregulation of nucleotide synthesis and cell adhesion pathways.

INTRODUCTION

The transcriptomic characteristics of + non-small cell lung cancer (NSCLC) represent a crucial aspect of its tumor biology. These features provide valuable insights into key dysregulated pathways, potentially leading to the discovery of novel targetable alterations or biomarkers.

METHODS

From The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, all available + (n = 10), + (n = 5) and + (n = 5) NSCLC tumor and + cell line (n = 7) RNA-sequencing files were collected. In addition, 10 healthy lung RNA-seq samples were included. Differential gene expression with DESeq2 (R package) and gene co-expression (WGCNA, R package) analyses were performed. Functional annotation was performed through Gene Set Enrichment Analysis (GSEA) using Webgestalt and RNAseqChef, Over-Representation Analysis (ORA) through Enrichr. iRegulon was used to identify enriched transcription factors that regulate a gene co-expression module.

RESULTS

• NSCLC samples were significantly enriched for the nucleotide synthesis and cell adhesion KEGG pathways compared to + and + samples. Moreover, was significantly downregulated in + NSCLC and PD-L1 was weakly expressed. When comparing + tumor versus cell line transcriptomes, an upregulation of and was found in cell lines together with a significantly decreased expression of , and . Within -tumors, was overexpressed in the - and -+ subgroups. The differential expression of and in cell lines was confirmed through RT-qPCR. Finally, the gene co-expression analysis unveils a gene cluster involving cell cycle-related genes which significantly correlates with the disease stage of patients. In addition, we propose and as key -specific transcription factors.

CONCLUSION

This study highlights cell adhesion and nucleotide synthesis as crucial signatures in + NSCLC. The upregulation of may serve as a prognostic biomarker, along with , a known mediator of bone metastases. Furthermore, and were identified as relevant transcription factors that could potentially regulate the biological processes in -rearranged NSCLC.