Pan-cancer Transcriptome Study Of Pediatric Renal Malignant Tumor

Purpose: Wilms’ tumor(WT),malignant rhabdoid tumor of kidney(RT)and clear cell sarcoma of kidney(CCSK)are the main three types of kidney malignancies in children.They have certain generality and specificity in pathogenesis,age of onset,pathological features,clinical manifestations,prognosis and treatment.This study aims to integrate the pan-cancer atlases of pediatric renal malignancies to reveal the biological commonness and specificity of pediatric renal tumors from the transcriptome level,and compare them with adult renal tumors,so as to clarify the pathogenesis of pediatric renal tumors and find a new direction for targeted therapy.Materials and Methods: Complete transcriptome data of 130 WT,58 RT and 13 CCSK were obtained from TARGET project.Total transcriptome data of 893 adult renal tumors,including539 clear cell carcinoma,289 papillary cell carcinoma,and 65 chromophobe cell carcinoma,were collected from the TCGA database.The control group consisted of 140 normal kidney tissues.The "DESeq2" package of R was used to calculate the differentially expressed m RNA,lnc RNA and mi RNA in various renal tumors and normal renal tissues.The "Cluster Profilerr" package was used for GO,KEGG pathway analysis and GSEA analysis of differentially expressed genes.Univariate Cox regression model,Lasso regression model and multivariate Cox regression model were used to construct the prognosis model of pediatric renal tumor.Results: The number of differentially expressed m RNA,lnc RNA and mi RNA,as well as their proportion in total RNA,were significantly higher in pediatric renal tumors than in adult renal tumors.GO functional enrichment showed that common differentially expressed genes in pediatric renal tumors were enriched in biological processes related to renal development.GSEA analysis showed that the biological processes of embryonic mesenchymal morphogenesis and metanephric mesenchymal development were significantly up-regulated in pediatric renal tumor tissues,while they were significantly down-regulated in adult renal tumor tissues.This difference in biological processes may be the key to the heterogeneity between pediatric and adult renal tumors.Survival analysis showed that the RNAs associated with the prognosis of WT,RT and CCSKwere different.Cox regression and Lasso regression were used to screen out prognostic related RNA and calculate the corresponding regression coefficients to construct the prognosis models of three kinds of pediatric renal tumor,respectively.Kaplan-Meier survival curve and Survival ROC assessment showed that the three prognostic models all displayed high risk stratification efficiency.Conclusion: This study reveals the commonality of molecular functions and biological processes of pediatric renal tumors at the transcriptional level,elucidates the heterogeneity between pediatric renal tumors and adult renal tumors,and clarifies the differences of prognostic related genes in three pediatric renal tumors,providing a new method for targeted therapy and clinical risk stratification of pediatric renal tumors.