Pathway enrichment analysis revealed that overrepresentation of dysregulated genes in various systems. Dysfunction of various systems may be complications of renal failure since kidneys are essential in the maintenance of homeostatic status. In addition, we also detected cancer-related pathways and GO items to be enriched with differentially expressed genes. The correlation between renal failure and cancer related biological processes may due to the dysfunction of cell cycle and DNA repair process in patients. Previous studies have demonstrated the enhanced expression of DNA repair-related proteins and induced cell cycle arrest at G1/S and G2/M in renal failure rats [
20‐
22]. Overrepresentation of dysregulated genes in the chronic myeloid leukemia (hsa05220) pathway revealed the similar gene expression of these two diseases which may explain the causative effect of lymphocytic leukemia on renal failure [
19]. These identified biological processes revealed the molecular signatures of renal failure.
To detect hub molecules, we constructed a network with proteins encoded by identified differentially expressed genes (Figure
2). Several hub molecules have been identified to play important roles in the progression of renal failure before. Take
RELA for example, protein encoded by this gene is NF-kappaB p65. In consistent with our results, detection of NF-kappaB p65 based on immunohistochemical staining and ELISA suggested that NF-kappaB p65 in rat glomeruli of multiple organ failure was significantly higher than that of control group [
23]. Attenuation of NF-kappaB p65 activation is effective in reducing endotoxic kidney injury [
24]. Inhibition of inflammation through NF-κB also reduced renal dysfunction caused by sepsis in mice [
25]. The involvement of NF-kappaB p65 in renal failure may be due to its interaction with inflammatory chemokines [
26], such as CXCL16, which was increased in active nephrotic syndrome patients and correlated with blood lipids, urine protein and inflammation responses [
27]. Genes involved in regulation of cell cycle,
TP53 and
CDK2, were also identified as hub genes. Their involvements in renal failure through regulation of G1 cell cycle arrest were reported before [
28]. Moreover, paricalcitol could prevent cisplatin-induced renal injury by suppressing the up regulation of
TP53 and
CDK2[
29]. Therefore, our study confirmed that these three genes may serve as potential targets for renal failure treatments. For the rest four hub genes,
SRSF1,
CAND1,
SMURF1, and
YWHAE, no previous report of their association with renal failure has been proposed before. Protein encoded by
SRSF1 is a member of the arginine/serine-rich splicing factor protein family. Up regulation of SRSF1 could increases the cellular pool of active p53 [
30], suggesting the implication of SRSF1 in renal failure through its regulation of the p53. For
SMURF1, protein encoded by this gene is an ubiquitin ligase that is specific for receptor-regulated SMAD proteins. It is reported that reduction of Smad7 due to the overexpression of Smurf1 in unilateral ureteral obstruction kidneys plays an important role in the progression of tubulointerstitial fibrosis [
31], which a harmful process leading inevitably to renal function deterioration. Consistently, our analysis detected the up regulation of
SMURF1, suggesting it may contribute to the progression of renal failure through its ubiquitination of SMAD7. Protein encoded by
YWHAE belongs to the 14-3-3 family of proteins which mediate signal transduction by binding to phosphoserine-containing proteins. Quantitative protein expression profiling revealed that overexpression of YWHAE prompt the proliferation of renal cancer cells [
32]. CAND1 may also promote the progression of renal cell carcinoma through its interaction with carbonic anhydrase IX [
33]. Whether the up regulation contributes to the pathogenesis of renal failure needs further investigation.