Gene Expression Profiling and Pathway Enrichment Analysis in Long-Term Survivors after Lung Transplantation with Normal Allograft Function

Abstract

Chronic lung allograft dysfunction (CLAD) is the main limiting factor for long-term survival after lung transplantation (LT). However, there is a small number of LT patients which are long-term survivors with good allograft function (LTS). The aim of the present study was to compare the gene expression profile of CLAD and LTS patients and performing an enrichment analysis by using Reactome annotation database. We analyzed whole-blood gene expression profiles of 60 double lung transplant recipients who were included in this multicenter cross-sectional study: 30 patients with CLAD and 30 patients with a stable allograft function 10 years after lung transplantation (LTS). Expression analysis were performed by microarray technology (ClariomTM D Arrays). We identified 458 differentially expressed genes (DEGs) between LTS and CLAD patients. Among them, 201 genes were up-regulated and 257 genes were down-regulated. Differentially expressed genes included MMP-8, LTF, TCN1 and OLFM4. Enrichment analysis showed involvement of neutrophil degranulation, class A/1 (Rhodopsin-like receptors), cell surface interaction at the vascular wall, antimicrobial peptides, interleukin-4 and 13 signaling, role of phospholipids in phagocytosis and activation of matrix metalloproteinases pathways. It seems that neutrophil degranulation, matrix metalloproteinases and antimicrobial peptides gene expression pathways within others could be involve in differences between CLAD and LTS patients. Study financed by Instituto de Salud Carlos III (PI13/01076); the European Regional Development Fund (FEDER), FUCAP, Astellas, Novartis and Chiesi.