Purpose: As a typical hypervascular tumor, clear cell renal cell carcinoma (ccRCC) is the most common type of RCC. This study was aimed to explore the prognostic genes for ccRCC, focusing on the roles of vascular endothelial growth factor A (VEGFA ) and Delta-like ligand 4 (DLL4 ) in the disease.
Materials and methods: The mRNA-sequencing data of kidney renal clear cell carcinoma (KIRC) were obtained from The Cancer Genome Atlas (TCGA) database, including 469 tumor samples and 68 adjacent normal samples. Using limma package, differentially expressed genes (DEGs) were analyzed by differential expression and subgroup analyses and confirmed using validation dataset GSE53757. Followed by enrichment analysis, protein–protein interaction (PPI) network analysis and protein subcellular localization were performed using multifaceted analysis tool for human transcriptome tool, and Cytoscape software and InnateDB database, respectively. Moreover, survival analysis was conducted to identify key prognosis-associated genes. In addition, VEGFA  and DLL4  levels were detected using real-time quantitative PCR (qRT-PCR).
Results: A total of 1,984 DEGs were screened in the KIRC tumor samples. VEGFA  was located in extracellular space and could interact with placental growth factor (PGF) and angiopoietin 2 (ANGPT2) in the PPI network. Subgroup analysis suggested that VEGFA  was significantly upregulated in stages I, II, and III ccRCC tumor samples. Survival analysis showed that TIMP1  was among the top four prognosis-associated genes. qRT-PCR analysis confirmed that the expression levels of DLL4  and VEGFA  were significantly upregulated in tumor samples.
Conclusion: VEGFA  and DLL4  might be prognostic genes for ccRCC. Besides, PGF , ANGPT2 , and TIMP1  might also be related to the prognosis of ccRCC patients.
Keywords: clear cell renal cell carcinoma, differentially expressed genes, protein–protein interaction network, subgroup analysis, survival analysis