Upregulation of IGF2BP2 Promotes Oral Squamous Cell Carcinoma Progression That Is Related to Cell Proliferation, Metastasis and Tumor-Infiltrating Immune Cells.

Wenhui Liu,Dongsheng Yu,Lijie Zhou,Shuai He,Hongyu Li,Hongshi Cai,Enjiu Pan

doi:10.3389/fonc.2022.809589

Abstract

The strong invasive and metastatic abilities of oral squamous cell carcinoma (OSCC) cells in the early stage are the main reason for its poor prognosis. The early diagnosis and treatment of OSCC may reduce the metastasis rate and improve the survival rate. The aim of this study was to explore candidate biomarkers related to the prognosis and progression of OSCC. We performed weighted gene coexpression network analysis to identify key modules and genes associated with OSCC and intersected the differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA)-OSCC and GSE30784 datasets. Next, we performed survival analysis and immunohistochemistry to screen and validate the hub gene insulin-like growth factor 2 (IGF2) mRNA binding protein 2 IGF2BP2. We also used TCGA pan-cancer data to verify that IGF2BP2 was expressed at high levels in a variety of cancers and was related to a poor prognosis in patients. Furthermore, we divided patients with OSCC into high and low expression groups based on the median expression level of IGF2BP2. Gene set enrichment analysis (GSEA) showed that IGF2BP2 led to a poor prognosis in OSCC by affecting cancer-related (epithelial-mesenchymal transition, glycolysis, cell cycle, etc.) and immune-related biological functions and pathways. Single-sample GSEA (ssGSEA), CIBERSORT, and xCell algorithms helped reveal that high IGF2BP2 expression was accompanied by a significant reduction in the immune score, stromal score, and microenvironment score and a decrease in the number of infiltrating CD8+ T cells in OSCC. In addition, silencing IGF2BP2 suppressed the proliferation, migration, and invasion of OSCC cells. In general, IGF2BP2 is a potential biomarker for the progression, immunotherapy response, and prognosis of OSCC.

Highlights

Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of oral cancers and has a high degree of malignancy; it can rapidly invade tissues and readily form metastases in the cervical lymph nodes and distant sites [1, 2]
Three candidate genes were found to be significantly associated with the overall survival (OS) of the patients in The Cancer Genome Atlas (TCGA)-oral squamous cell carcinoma (OSCC) dataset by applying univariate Cox regression analysis (Figure 3D)
Only ANO1 and IGF2BP2 had statistically significantly associated with the OS of patients with OSCC in both datasets

Summary

Introduction

Oral squamous cell carcinoma (OSCC) accounts for approximately 90% of oral cancers and has a high degree of malignancy; it can rapidly invade tissues and readily form metastases in the cervical lymph nodes and distant sites [1, 2]. With the rise of high-throughput sequencing technology, a large number of omics datasets [such as those in The Cancer Genome Atlas (TCGA) database Cancer.gov/tcga)] have been generated, and the Gene Expression Omnibus (GEO) database Weighted gene coexpression network analysis (WGCNA) is a systems biology method suitable for complex multisample data analysis. It can assess the expression relationship between genes, construct a coexpression network, identify gene modules consisting of highly coexpression genes, and combine gene modules. WGCNA can identify gene modules that are highly related to the malignant progression of OSCC to explore the genes and biological processes that have changed in OSCC patients and normal controls

Objectives

Methods

Results

Conclusion