Highly expression of MYBL2 is correlated with a poor prognosis and immune infiltration in clear cell renal carcinoma

Background:Clear cell renal carcinoma(ccRCC)is notorious for its highly unfavorable prognosis,closely related to immune cell infiltration(ICI).MYB Proto-Oncogene Like 2(MYBL2)is elevated in multiple types of human cancer and is recognized as a crucial role in tumorigenesis.In the present study,we aimed to determine the roles of MYBL2 in the prognostic outcomes of ccRCC.Methods:We analyzed the GSE100666 dataset from the Gene Expression Omnibus(GEO)database and found that the expression of MYBL2 was significantly higher in ccRCC subjects than in normal controls.Next,RNA sequencing data related to ccRCC were retrieved from The Cancer Genome Atlas(TCGA)database and the levels of MYBL2 were compared between tumor and peri-tumor tissues.The correlation between MYBL2 and clinicopathological parameters was assessed by logistic analysis.The Kaplan-Meier method,Cox-regression analysis,and nomograms,were applied to investigate the potential clinical benefits of MYBL2 in ccRCC.We also evaluated the correlation between MYBL2 and immune cell infiltration with a single-sample gene set enrichment analysis(ssGSEA).The association between MYBL2 and immune checkpoints was determined via the TIMER and TISIDB databases.Finally,correlation analysis was conducted to predict upstream non-coding RNAs(ncRNAs)regulating MYBL2,and a completing endogenous RNA(ceRNA)network was constructed to visualize the long non-coding RNAs(lncRNAs)-microRNAs(miRNAs)-MYBL2 axis in ccRCC.Finally,further analysis of upstream lncRNAs was carried out to validate the accuracy of the network.Results:MYBL2 was significantly over-expressed in ccRCC(P<0.001).High levels of MYBL2 expression in ccRCC correlated with a worse T stage,a more advanced N stage,a higher M stage,a more deleterious pathological stage,and higher histological grades.MYBL2 was identified as a risk factor for disease-specific survival(hazard ratio(HR)=2.73,P<0.001),overall survival(HR=1.91,P<0.001),and progression-free interval(HR=2.03,P<0.001).MYBL2 also positively associated with multiple types of immune cells and checkpoints.Finally,two ceRNA axes,PVT1-miR-30e-5p-MYBL2 and LINC00511-miR-29c-3p-MYBL2 were detected as the most promising upstream ncRNAs regulating MYBL2 in ccRCC,and we also validated the expression of MYBL2 and PVT1 by launching qRT-PCR.We found that the expression of MYBL2 was significantly higher in 786-O than in human kidney-2 cell line HK-2(P<0.001)and the expression of PVT1 was significantly higher in Caki-1 than in HK-2(P<0.001).Conclusion:Our study revealed that ncRNAs might upregulated the expression of MYBL2 in ccRCC and that this was associated with an unfavorable prognosis and immune infiltration.