Integrative meta-analysis of publically available microarray datasets of several epithelial cell lines identifies biological processes affected by silver nanoparticles exposure.

The present study aimed to identify differentially expressed genes (DEGs) under silver nanoparticle (AgNPs) treatment. We used a meta-analysis approach to integrate four publicly available microarray datasets, containing control and epithelium samples treated by either AgNPs- or Ag ions. The Fisher's method combined p-values of studies. Post hoc analyses including protein-protein interaction (PPI) and the overrepresentation test were conducted. Analytical results identified 1652 DEGs associated with AgNPs exposure. The most significant up-regulated genes, including MT1H, MT1X, and MT2A were metallothionein family members. The most significant down-regulated gene, TM4SF5, is a novel biomarker for AgNPs exposure. The PPI network analysis revealed that a member of the heat shock protein family, HSP90AA1, is the top up-regulated "hub" gene. Up-regulation of heat shock proteins and metallothionein genes is part of a cellular response to oxidative stress induced by AgNPs treatment. Interestingly, AgNPs may interact negatively with blood coagulation and amino acid metabolism systems.