Differential gene expression analysis for the identification of potential biomarkers for Niemann-Pick type C disease.

Abstract

Niemann-Pick disease (NP) is a rare neurovisceral lysosomal lipid storage disorder. NPC (NP type C) is characterized by the accumulation of unesterified cholesterol and other lipids within the cell, the function of lysosomes usually is impaired as well as the autophagy flux. To better understand the molecular pathways affected in this disease, we perform a bioinformatic study. We used in silico methods to identify genes affected in this disease. The first approach was an analysis of microarray data from the public archive GEO2, accession number GSE124283. We studied gene expression of skin fibroblast from 55 individuals, 22 healthy controls (13 males and 9 females) and other 23 with NPC (12 males and 11 females), 16 patients suffering from infantile NPC, 5 juvenile NPC and 2 adults. The differential expression analysis was performed using limma package, genes with significative adjusted p value and fold change > 0.5 and < -0.5 were selected, we used topGO package to obtain the Gene Ontology. The analysis revealed that cellular components enriched were vesicle membrane, vacuolar lumen lysosome, cytoplasm vesicle, cytoskeletal fiber, nucleus and nucleoplasm. For molecular function were affected catalytic activity, cadherin binding and enzyme binding, and the biological process enriched were the phagosome maturation, lysosome organization, vesicular transport, apoptotic process, gene expression, proteosome-mediated ubiquitin, cell cycle, cellular macromolecule biosynthetic process and regulation of cellular response to stress. Our results were consistent with changes in cell homeostasis reported from NPC patients. Abnormal protein degradation and metabolism might contribute to the higher level of mortality in this disease. We propose that some of the DEGs that are more related to NPC disease according to our study, could have value as potential biomarkers of this disease helping to unravel the molecular mechanisms involve in this disease.