Prognostic Value Of RNA Binding Protein PCF11 In Oral Squamous Cell Carcinoma

Background:RNA binding proteins(RBPs)play important roles in tumor carcinogenesis and progression.However,the role and mechanism of RBPs in the tumorigenesis and development of oral squamous cell carcinoma are still unclear.This study was aimed to explore the potential value of RBPs related genes in evaluating the prognosis of OSCC,and to provide assistance in predicting the prognosis of OSCC.Materials and methods:The transcriptome data and clinical follow-up data of OSCC patients were downloaded from The Cancer Genome Atlas(TCGA)database,and the differentially-expressed RBPs were screened out via R software.Then,the interactions between these differentially-expressed RBPs were explored through Protein-Protein Interaction(PPI)network.After the functional enrichment analysis in differentially-expressed RBPs,the prognostic RBPs of OSCC were obtained through univariate Cox regression analysis.Meanwhile,a prognostic model was constructed via multivariate Cox regression analysis,and various bioinformatics analyses such as survival analysis,Receiver Operating Characteristic curve(ROC)analysis,independent prognostic analysis and drug sensitivity analysis were performed.After that,the prognosis related RBPs were screened out and then verified by other cohorts from Gene Expression Omnibus(GEO)database.In the end,the expression of target RBP,was investigated in OSCC cell lines(SCC9,SCC15 and SCC25)and in 84 OSCC patients.Results:A total of 249 OSCC related differentially-expressed RBPs were screened out in the TCGA database and the Protein-Protein Interaction network were constructed.Functional enrichment analysis showed that these differentially expressed RBPs were mainly located in cytoplasmic ribosomes and spliceosomal complex,and involved in biological processes such as RNA transport,RNA catabolic process,RNA splicing and ncRNA processing.Subsequently,univariate Cox regression analysis indicated that there were 7 RBPs related to the prognosis of OSCC patients,and a prognostic model and a nomogram were constructed based on 5 RBPs.In addition,we explored the sensitivity of 30 clinical common anti-tumor drugs in OSCC based on the prognostic model,and found that drugs such as methotrexate and gefitinib have significant medication value for the patients in high-risk and low-risk groups respectively,which provided a certain reference for clinical medication.After that,5 RBPs were screened out through survival analysis and then validated with OSCC cohorts from the GEO database.It was showed that only PCF11(PCF11 Cleavage And Polyadenylation Factor Subunit)was found to be significantly differentially-expressed in OSCC.Meanwhile,Gene Set Enrichment Analysis showed that the low expression of PCF11 in OSCC was related to the enhancement of oxidative phosphorylation(OXPHOS)and proteasome.In the end,PCF11 was confirmed to be down-regulated in OSCC cell lines and tissues by PCR and immunohistochemistry.Conclusion:PCF11 is a potential prognostic biomarker in OSCC.Evaluating the expression level of PCF11 in OSCC might provide assistance in predicting the prognosis of OSCC.