Changes of gene expression in peripheral blood mononuclear cells of lung cancer patients with or without anorexia

Abstract

Anorexia is a disabling symptom in cancer and we aimed at investigating the role of changes in gene expression in lung cancer patients presenting with anorexia. Genome-wide transcriptomic profiling was assessed in PBMCs RNA from newly diagnosed lung cancer patients and in a control group. RT-qPCR was used for selected genes. RNA-Seq analysis revealed among groups a large number of differentially expressed genes mainly implicated in immune system regulation, oxidative stress and cytokine-mediated inflammation signaling pathways. In particular, we identified a total of 983 DEGs (843 up-regulated; 140 down-regulated) in anorexic cancer compared to controls. A selected number of DEGs including ADAM8, SMAD4, CCR4 and CLU were differentially expressed within cancer group according to the presence/absence of anorexia. In terms of RT-qPCR, ADAM8 was less expressed in cancer patients than controls (p<0.001), and in anorexic patients vs controls (p=0.001). The expression of SMAD4 was lower in cancer vs controls (p=0.005), and in anorexic patients vs controls (p=0.009). We observed lower CCR4 expression in both anorexic and non-anorexic vs control (p=0.004, p=0.011, respectively) and a similar trend was present for CLU. Our data shed new light on the role of specific genes and their associated molecular pathways as potential key mechanisms for the development of anorexia and may represent a novel landmark for understanding the complex pathophysiology of impaired appetite in cancer.