Comprehensive Characterization Of The RRNA Metabolism-related Genes In Human Cancer

Cancer is a leading cause of death in both developing and developed countries.Between both sexes,colorectal,lung,breast,prostate,stomach and liver cancers are the most commonly diagnosed and the leading causes of cancer death.In order to gain analytical breadth,and define commonalities,differences and emergent themes across human cancers,Pan-cancer analysis is beginning to be used in cancer research.Panancer analysis of specific function and pathway genes has been reported in recent years,which provides a unique,comprehensive,in-depth,and interrelated understanding of human cancer.Ribosomal RNA(rRNA)metabolic process is critical for protein synthesis and increased protein synthesis is required for tumorigenesis.rRNA metabolism-related genes are defined as genes associated with the chemical reactions and pathways involved in rRNA.Recent studies have demonstrated that rRNA metabolic related genes are dysregulated and can predict prognosis in human cancer.However,comprehensive and systematic analysis of rRNA metabolic related genes in human cancer has not yet been explored.Here,a Pan-cancer analysis of rRNA metabolic related genes shows the landscape of these genes in cancer tissues and cells.In this study,we displayed the mRNA expression,mutation,DNA methylation,copy number variation(CNV)and clinical landscape of rRNA metabolic related genes in human cancer.To study rRNA metabolism-related genes across human cancers,an rRNA metabolism-related gene set was defined based on GO and MSig DB,287 of these genes matched the data from the TCGA.We found that the rRNA metabolic process was active in tumor samples due to rRNA metabolism-related genes and that the rRNA metabolic process is active in multiple cancers.We identified 83 rRNA metabolism-related genes that were significantly upregulated in more than half of 16 cancers,suggesting that these genes may be functionally conserved in cancer.These 83 genes were defined as functionally conserved upregulated rRNA metabolism-related genes.We found 54 of these genes were upregulated in all five digestive system cancers(CRC,LIHC,CHOL,STAD and ESCA)and 64 genes were upregulated in both two respiratory system cancers(LUAD and LUSC).These results suggested that rRNA metabolism-related genes are specific biomarkers in digestive and respiratory system cancer.Our result relevead that rRNA metabolism-related genes upregualtion is caused by CNV gains rather than by DNA hypomethylation or mutation.For all the genes we tested,including functionally conserved upregulated genes,15/16 types of cancer have a high proportion of mutation rate of 1 and 1%–3%.We found that 89.8% of the functionally conserved upregulated rRNA metabolism-related genes had no DNA hypomethylation in any cancer and that 6.3% were only present in one cancer.Most functionally conserved upregulated genes were not accompanied by DNA hypomethylation.We identified 41 functionally conserved rRNA metabolism-related genes that were driven by CNV across 16 cancers.A total of 36.5% of functionally conserved upregulated genes were driven by CNV in a single cancer,whereas 63.5% of genes were driven by CNV in at least two cancers.These results indicate that CNV is an important mechanism for regulating rRNA metabolism-related gene expression in human cancer.rRNA metabolism-related gene upregulation is associated with poor prognosis and essential for cancer cell growth.We observed that active rRNA metabolic process was correlated with poor five-year overall survival and progression-free survival.A series of analyses were performed to investigate clinical relevance for each CNV-driven rRNA metabolism-related gene.Our results indicated that binary logistic regression models based on TNM staging indexes and CNV-driven rRNA metabolism-related genes with clinical relevance were good indicators for prognoses and survival in CRC,LUAD and KIRC.Furthermore,CNV-driven rRNA metabolism-related genes with clinical relevance are essential for cancer cell growth.Finally,functional experiments confirmed the oncogenic roles of EXOSC8 in colorectal carcinoma.Collectively,our comprehensive Pan-cancer analysis of rRNA metabolism-related genes illustrates the characterization of these genes in cancer tissues and cells.Our data suggest that rRNA metabolism-related genes play an important role in tumorigenesis.Moreover,rRNA metabolism-related genes could serve as a valuable new biomarker,prognostic factor,and a potential target for newtreatment strategies.