Introduction

We assessed differences in gene expression pathways in patients with EGFR-mutated non-small cell lung cancer (NSCLC), focusing on differences between patients < 70 years old vs. ≥ 70 years old at diagnosis given the wide range of ages presenting with EGFR-mutated lung cancer.

Methods

281 patients were identified using the Tempus Lens database. A differential gene expression analysis for the two age groups was performed using comprehensive RNAseq data, with the top 1% of genes used to generate enhanced volcano plots using the edgeR package in Bioconductor. A Gene Set Enrichment Analysis was performed using the KEGG reference database for modulated genes with adjusted p≤0.05. All reported enrichments scores (ES) have an adjusted p≤0.05.

Results

137 patients were < 70 years old and 144 patients were ≥ 70 years old at diagnosis. Significant differences in gene expression were found between the two groups (Figure 1). Changes in biological pathways, as defined by the KEGG reference database, are depicted (Figure 2). Of particular interest, in patients ≥ 70 years old compared to < 70 years old, there was general up-regulation of cortisol and aldosterone synthesis and secretion (ES=1.47 and 1.41, respectively; both p≤0.005) with concomitant up-regulation of processes involved in Cushing’s syndrome (ES=1.40; p≤0.002). Down-regulation of both lipid mobilization and carbohydrate metabolism (glycolysis and gluconeogenesis) were also observed. Disruption of circadian processes were associated with cortisol secretion and Cushing’s disease, however there was no evidence of primary circadian pathway disruptions.

Conclusions

Significant differences in gene expression and upregulated pathways were observed when stratifying patients by age, with an upregulation of pathways involved in cancer cachexia and inflammation seen in those age ≥ 70 years old at diagnosis. RNA sequencing serves as a promising tool to help us translate biologically relevant genomic features to clinical features in patients with EGFR-mutated lung cancer.

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