Identification of key genes CCL5, PLG, LOX and C3 in clear cell renal cell carcinoma through integrated bioinformatics analysis

Abstract

Abstract Background Clear Cell Renal Cell Carcinoma (ccRCC) is a malignant tumor with high mortality and recurrence rates and the molecular mechanism of ccRCC genesis reminds unclear. In this study, we screen out several key genes associated with the prognosis of ccRCC by using integrated bioinformatics. Methods Two ccRCC expression profiles were downloaded from GEO and one dataset was gained from TCGA. RRA method was used to analyze the three datasets to gain integrated differentially expressed gene (DEGs) by comparing ccRCC with normal tissues. The GO functional annotation and KEGG pathway analysis were performed to analyze the potential functions of these DEGs. The STRING and Cytoscape were used to construct PPI network and module analyses to screen the hub genes. The expression of hub genes was analyzed using GEPIA, followed by RT-qPCR and IHC to validate the expression of hub genes between ccRCC and adjacent normal tissues. Finally, the prognostic value of these hub genes for ccRCC patients were identified by K-M plotter. Result 125 DEGs were identified by using the limma package and RRA method, which include 62 up-expressed genes and 63 down-expressed genes.GO analysis showed that the up-expressed genes were primarily enriched in signal transduction, immune response and cell-cell signaling. The down-expressed genes were primarily enriched in ion transmembrane transport, excretion and transport. The top five enriched pathways gained from the KEGG pathway analysis were complement and coagulation cascades, aldosterone-regulated sodium reabsorption, collecting duct acid secretion, PPAR signaling pathway and prion diseases. K-M plotter and GEPIA database were utilized to make clear that CCL5, LOX and C3 are not only up-expressed in ccRCC, but also had a connection with the poor prognosis of ccRCC. PLG is down-expressed in ccRCC, which associated with the better prognosis of ccRCC. RT-qPCR and IHC assays also confirmed the differential expression of these four hub genes in paired ccRCC and adjacent normal tissues. Conclusion These findings manifest that CCL5, LOX, C3 and PLG may play key roles in the progression and prognosis of ccRCC, which will be helpful for further studies to find the potential therapeutic targets and underlying mechanisms of ccRCC.