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

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.

Cytoplasmic IGF2BP2 Protein Expression in Human Patients with Oral Squamous Cell Carcinoma: Prognostic and Clinical Implications

“…Univariate and multivariate analyses both identified IGF2BP2 expression, histological grade, T status, lymph node metastases, and disease stage as key independent prognostic factors impacting the overall survival of OSCC patients (Table 3 ). Our findings suggest that IGF2BP2 may operate as an oncogene in OSCC cells, which is in line with earlier research 34 , 35 . Note that this was the first study to examine the use of clinicopathological variables and IGF2BP2 protein expression within the context of OSCC prognosis.…”

“…We also determined that IGF2BP2 overexpression is related to poor overall survival outcomes in OSCC patients (Figure 2 ), which suggests that it could perhaps be used as a prognostic indicator for use in OSCC risk classification. Elevated IGF2BP2 expression in OSCC cells has been linked to cell proliferation, metastasis, and tumor-infiltrating immune cells in in vitro experiments 34 . Those studies confirm our clinical results, which suggest that IGF2BP2 enhances OSCC epithelial cell proliferation and epithelial-mesenchymal transition (EMT), thereby promoting tumor growth and invasion in OSCC patients.…”

“…The overexpression of IGF2BP2 has also been shown to promote the development of glioblastoma multiforme by activating the IGF2/phosphoinositide 3-kinase (PI3K)/Akt pathway, thereby making glioblastoma resistant to temozolomide therapy [32]. In head and neck squamous cell carcinoma and OSCC tissues, the elevated mRNA or protein expression of IGF2BP2 is indicative of poor prognosis [33][34][35]. The upregulation of IGF2BP2 has also been shown to promote OSCC progression associated with cell proliferation, metastasis, and tumor-infiltrating immune cells [34].…”

“…In head and neck squamous cell carcinoma and OSCC tissues, the elevated mRNA or protein expression of IGF2BP2 is indicative of poor prognosis [33][34][35]. The upregulation of IGF2BP2 has also been shown to promote OSCC progression associated with cell proliferation, metastasis, and tumor-infiltrating immune cells [34].…”

Methyltransferase‐like 3 promotes cervical cancer metastasis by enhancing cathepsin L mRNA stability in an N6‐methyladenosine‐dependent manner

“… 53 We first found that IGF2BP2 directly bound to the m6A sites in the CTSL 5′‐UTR and enhanced CTSL mRNA stability in an m6A‐dependent manner. Previous studies have shown that increased IGF2BP2 expression levels promote the metastasis of oral squamous cell carcinoma 54 and gastric cancer. 55 Here, we revealed the oncogenic role of IGF2BP2 in cervical cancer metastasis and its regulatory effect on CTSL mRNA stability to enhance cervical cancer progression.…”