• Xilong Wang, Jun Zhang, Yang Wang, Yangyun Wang, Wandong Yu, and Guowei Shi.
• Department of Urology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200240, China.
• Am. J. Med. Sci. 2022 Aug 1; 364 (2): 220-228.

BackgroundDelta-like canonical notch ligand 4 (DLL4) is considered a potential prognostic gene for renal cell carcinoma (RCC). We assessed the molecular mechanisms and novel biomarkers associated with DLL4 during RCC development.MethodsFour gene expression profiles were downloaded from the GEO database. Differentially expressed genes (DEGs) were identified between RCC and normal renal samples, including common DEGs (co-DEGs). Thereafter, RCC-associated gene exploration was performed and a PPI network was constructed to identify the core genes. Survival analysis of core genes in the high expression group (H group) and low expression group (L group) was also performed. The key genes related to the core genes were investigated, and the miRNA-target genes and TFs-target genes were analyzed. Finally, the expression levels of VEGFA, FLT1, EGLN3, and DLL4 in RCC and paracancerous tissues were determined.ResultsA total of 11,867 DEGs and 622 co-DEGs were identified in this study, and 67 RCC-associated genes that were mainly enriched in signal transduction and angiogenesis function were further explored. VEGFA was identified as the core gene. Further, 30 DEGs and 9 DE-miRNAs were identified between the H and L groups. VEGFA was positively correlated with 19 genes, including EGLN3, FLT1, and DLL4. A total of 18 miRNA-target interactions, including miR-134-5p-DLL4, were obtained. VEGFA, FLT1, EGLN3, and DLL4 were significantly expressed in RCC tissues compared with paracancerous tissues.ConclusionsDLL4 may contribute to the development of RCC by participating in signal transduction and angiogenesis. VEGFA, FLT1, EGLN3, DLL4, and miR-134-5p may be novel biomarkers for RCC.Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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