Network spatio-temporal analysis predicts disease stage-related genes and pathways in renal cell carcinoma

Abstract

ABSTRACT. The purpose of this study was to screen the key genes and pathways of renal cell carcinoma (RCC) and lay the foundation for its diagnosis and therapy. Microarray data of normal subjects and RCC patients at different stages of disease were used to screen differentially expressed genes (DEGs). Based on the DEGs in the four disease stages, four co-expression networks were constructed using the Empirical Bayes method and hub genes were obtained by centrality analysis. The enriched pathways of the DEGs and the mutual hub genes in the cluster of each disease stage were investigated. The mutual hub genes of the four disease stages in RCC tissue were validated using reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. A total of 432 DEGs were screened, including 233 upregulated and 199 downregulated genes, by statistical analysis. Centrality analysis of co-expression networks in different disease stages suggested that PLXDC1, IKZF1, RUNX2, and RNF125 were mutual hub genes. Pathway analysis showed that the DEGs were significantly enriched in seven terms. The hub modules in stage I disease were significantly enriched in the complement coagulation cascade pathway and the hub modules of the other three disease stages were enriched in natural killer cell-mediated cytotoxicity. The expression levels of PLXDC1, IKZF1, RUNX2, and RNF125 were significantly different between normal subjects and RCC patients by RT-PCR and western blot. Our study revealed four hub genes (PLXDC1, IKZF1, RUNX2, and RNF125) and two biological pathways that might be underlying biomarkers involved in RCC.

A plasma membrane protein based prognostic model in clear cell renal cell carcinoma

“…Then, the TF-PMP network shows that transcription factors FOXM1, NCAPG, CENPA, MYBL2, EOMES, IRF4, IKZF1 and BATF are closely related to these PMPs. Some previously studies have shown those TFs were connected with occurrence and progression of ccRCC [12][13][14][15][16][17][18]. Base on the above ndings, we have good reason to believe that those PMPs play a signi cant role in ccRCC as a whole.…”

Receptors that bind to PEDF and their therapeutic roles in retinal diseases

“…Plexin domain-containing 1 (PLXDC1), also known as tumor endothelial marker 7, is a member of the tumor vascular endothelial marker family ( 143 ). The genes encoding PLXDC1 are highly expressed during tumor angiogenesis and enriched in many types of tumor endothelial cells ( 144 ), including glioblastoma endothelium ( 57 , 63 ), ovarian cancer ( 62 ), gastric cancer ( 60 ), renal cell carcinoma ( 61 ), colorectal cancer ( 64 ), lung cancer ( 58 ), breast cancer ( 56 ), and osteosarcoma ( 59 ). PLXDC1 has been found to be highly expressed in the endothelial cells in the ocular disease DR context and is highly specific to diseased blood vessels ( 145 ).…”