Diagnostic Significance And Prognostic Value Of The RNA-binding Protein IGF2BP2 In Head And Neck Squamous Cell Carcinoma

Objective: Head and neck squamous cell carcinoma(HNSC)is a kind of malignant tumor with high incidence and poor prognosis.Although the treatments for HNSC are improving continuously,there was no significant improvement in the survival of patients.In recent years,RNA binding proteins(RBPs)have been demonstrated to be abnormally expressed in various tumors and related to tumorigenesis and progression.However,there are still few studies on the role of RBPs in HNSC.The purpose of this study was to identify differentially expressed RBPs in HNSC and their diagnostic value and prognostic significance,and to further explore the potential molecular mechanisms of IGF2BP2,as an independent risk factor for patients’ survival.Methods: The differentially expressed RBPs between HNSC and normal tissues were identified based on three HNSC transcriptome datasets(TCGA,GSE30784,GSE9844).Diagnostic value was evaluated by the receiver operating characteristic curve(ROC).Furthermore,independent prognostic risk factors were screened from upregulated RBPs using Kaplan-Meier survival analysis,univariate and multivariate Cox regression analysis;the protein expression of IGF2BP2 in 6 pairs of HNSC and adjacent samples was detected by Western blot;DNA methylation of IGF2BP2 was analyzed in the TCGA dataset;the relationship between IGF2BP2 expression and pathological features was explored;GSEA,IGF2BP2 target RNA prediction and prognosis analysis were used to explore the potential molecular mechanisms of IGF2BP2 in the biological process of HNSC.Results: Compared with normal tissues,10 abnormally expressed RBPs were identified in HNSC by differential analysis in 3 cohorts.ROC analysis showed that the AUC values of RSRC1 and IGF2BP2 were both greater than 0.9.IGF2BP2 mRNA was upregulated in HNSC tissues and is an independent risk factor for the prognosis of patients.Western blot showed that IGF2BP2 protein was also highly expressed in HNSC.There was a significant negative correlation between RNA expression level of IGF2BP2 and methylation level of the cg12781915 site.Correlation analysis of clinicopathological features,GSEA analysis,prediction of IGF2BP2 target RNA and prognosis analysis all indicated that IGF2BP2 related to HNSC progression to some extent.Conclusions:RSRC1 and IGF2BP2 can serve as two new biomarkers for the diagnosis of HNSC.IGF2BP2 plays an important role in the development of HNSC and is expected to become a prognostic marker and therapeutic target for HNSC.