Abstract
The molecular heterogeneity of primary clear cell renal cell carcinoma (ccRCC) has been reported. However, the classifications of Von Hippel–Lindau (VHL) mutant ccRCC are unclear. Here, VHL mutant ccRCC from The Cancer Genome Atlas and E-MTAB-1980 datasets were divided into two sub-clusters through non-negative matrix factorization algorithm. Most VHL mutant ccRCC patients in sub-cluster2 were with pathological T1 stage and VHL mutant ccRCC patients in sub-cluster1 were with decreased overall survival. DNA replication and homologous recombination scores were higher, while, WNT signaling pathway and regulation of autophagy scores were lower in sub-cluster1 VHL mutant ccRCC. Moreover, PBX1 transcriptional scores and mRNA expressions were lower in sub-cluster1 VHL mutant ccRCC patients and were associated with the overall survival of VHL mutant ccRCC. Furthermore, PBX1 associated genes EMCN and ERG were down-regulated in sub-cluster1 VHL mutant ccRCC and overall survival was decreased in EMCN or ERG lowly expressed VHL mutant ccRCC patients. Also, PBX1 and EMCN were down-regulated in ccRCC tissues, compared with normal kidney tissues. At last, we constructed risk models based on PBX1, EMCN and EGR expression features. With the increase of the risk score, the number of death of VHL mutant ccRCC patients was increased.
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