Bioinformatics Analysis On The Prognostic Role Of RNA Processing Factor SCAF8 In Renal Clear Cell Carcinoma

Background:Accurate RNA transcription is crucial for maintaining cell physiological function,and RNA polymerase II(RNAPII)is essential for m RNA synthesis.Dysregulation of RNA processing factors in cancer drives malignant cell status,which potentiates their attractive role as therapeutic targets to be explored.At present,there are many studies related to m RNA transcriptional initiation and its regulation,and their relevant impacts on cancer have been widely indicated.However,as the counterpart,post-initiation events of transcription has just been less discussed,especially in the transition between elongating and terminating PNAPII.Recently,two m RNA anti-terminators have been first identified.We observed that SCAF8,one of the serine/arginine rich-related and Cterminal repeat domain(CTD)-associated factors,draws widely alterations among cancers.SCAF4 and SCAF8 are required for correct m RNA transcript maturation through maintaining m RNA elongating and preventing m RNA transcript cleavage in early poly A sites.Studies suggested that aberrant expressions of SCAF4 or SCAF8 are associated with many diseases processes.RNA processing is found systematically regulated in cancer,and contributes to tumorigenesis and progression.Notably,a widespread intronic polyadenylation has been demonstrated responsible for inactivation of a cluster of tumor suppressors in leukemia.Hence,disfunction of m RNA anti-terminator may play an important role in cancer genome regulation.While as we known,no related researches have been reported.Here,we analyzed SCAF8 expression and found a profound reduction in kidney renal clear cell carcinoma(KIRC).Our study also indicated that SCAF8 loss altered a group of genes that might be related to poor KIRC prognosis.In conclusion,we recognized SCAF8 as a potential KIRC biomarker for prognosis,and indicated possible mechanisms influenced by SCAF8 loss in worse clinical outcome.Objective:In this study,we aimed to investigate the prognostic role of SCAF8 in KIRC by analyzing the expression of SCAF8,the genes and signaling pathways associated with loss of SCAF8,with KIRC patients as the object of bioinformatics analysis.Method:(1)Correlated clinicopathological information of KIRC patients and Pan-cancer were obtained from The Cancer Genome Atlas(TCGA)database(portal.gdc.cancer.gov).UALCAN(ualcan.path.uab.edu)was used to analyze m RNA expression and gene methylation status.c Bio Portal(cbioportal.org)was used to analyze SCAF8 genomic alterations and the correlation between SCAF8 m RNA expression and methylation status.(2)Wilcoxon rank sum test and Logistic regression analysis were used to compare and determine the correlation between SCAF8 expression and different clinicopathological characteristics in KIRC patients.(3)Receiver operating characteristic(ROC)and the Kaplan–Meier(K-M)plotter were used to compare overall survival(OS),disease specific survival(DSS)and progression free interval(PFI)between different subgroups in KIRC patients.Univariate and multivariate Cox regression analysis was used to determine SCAF8 expression as an independent risk factor in KIRC prognosis.(4)UALCAN and c Bio Portal were used to screen for genes correlated with SCAF8 expression alteration.Correlated genes of SCAF8 were performed for pathway enrichment analysis by Metascape(metascape.org).(5)R software(Version 3.6.3)and related packages were used for data analyzing and visualizing.P < 0.05 was considered significant threshold.Result:(1)SCAF8 is downregulated in KIRC and associated to clinical characteristics in KIRC patients.(2)Promoter methylation of SCAF8 significantly increased in KIRC tissues,and methylation levels of SCAF8 promoter showed negative correlation with SCAF8 m RNA expression.(3)SCAF8 is associated to clinical characteristics in KIRC patients,which displayed significant lower expression in T stage T3 and T4,N stage N1,M stage M1,clinical stages III-IV,and male sex patients.(4)SCAF8 shows a predictive value for KIRC diagnosis and prognosis,and lower SCAF8 expression was associated with poor overall survival(OS),disease specific survival(DSS)and progression free interval(PFI)in KIRC patients.(5)SCAF8 was highly related with crucial factors in KIRC ontogeny,and FABP6 and MFSD2A were negatively correlated with SCAF8 expression,indicating poor prognosis of KIRC patients.Conclusion:(1)Low SCAF8 expression indicates a poor KIRC prognosis.(2)SCAF8 shows a predictive value for KIRC diagnosis and prognosis.(3)SCAF8 was highly related with crucial factors in KIRC ontogeny,and FABP6 and MFSD2 A were negatively correlated with SCAF8 expression,indicating poor prognosis of KIRC patients.It provides a theoretical basis for further exploring the possible mechanisms of poor prognosis caused by SCAF8 loss.