Clinical Significance of an m6A Reader Gene, IGF2BP2, in Head and Neck Squamous Cell Carcinoma

Abstract

The importance of N6-methyladenosine (m6A) in tumor recurrence and prognosis has been recognized in recent years. The role of m6A readers, such as insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), in regulating head and neck squamous cell carcinoma (HNSCC) remains unclear. We, therefore, assessed the prognostic role of IGF2BP2 in HNSCC using openly available data from The Cancer Genome Atlas (TCGA) in conjunction with HNSCC patient sample immunohistochemistry (n = 36). The correlation between IGF2BP2 expression and clinical characteristics was then examined. The role of IGF2BP2 in prognosis was assessed by Kaplan-Meier curves and Cox analysis. Finally, TCGA data was used to explore possible carcinogenic mechanisms with multi-GSEA (gene set enrichment analysis). Analysis of TCGA data and IHC results revealed that IGF2BP2 was upregulated in HNSCC tumor tissues, and the expression level was related to the T stage. Simultaneously, Kaplan-Meier curves and Cox analysis indicated that highly expressed IGF2BP2 correlated with poor prognosis and that IGF2BP2 was a potential prognostic factor for HNSCC. Gene set enrichment analysis revealed that scavenging and degradation, synthesis and metabolism, cell growth, death and motility, and cancer pathways were differentially enriched in patients with high IGF2BP2 expression. Our results demonstrate that IGF2BP2 plays an important role in tumor progression and may serve as an important biological prognostic factor for HNSCC. Keywords: head and neck squamous cell carcinoma (HNSCC), insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), N6-methyladenosine (m6A), prognostic factor, tumor

The role of IGF2BP2, an m6A reader gene, in human metabolic diseases and cancers

“…However, available evidence demonstrates that IGF2BP2 targets GLUT1, promoting aerobic glycolysis and proliferation of PDAC cells [68,[75][76][77]. IGF2BP2 also promotes metabolism of esophageal cancer and HNSCC [16,67].…”

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“…Previous studies have shown that EZH2 silencing reduced cancer cell growth, migration and invasion in SCCHN (Liu et al, 2013;Chang et al, 2016), but which lack transgenic animal experiments and does not involve the influence of EZH2 on tumor microenvironment regulation of tumor genesis and development. IGF2BP2 overexpression was observed in pancreatic cancer, colorectal cancer, and SCCHN, which promoted cancer cell proliferation by activating the PI3K/Akt signaling pathway (Ye et al, 2016;Wang et al, 2019;Xu et al, 2019;Deng et al, 2020). These studies consistently with our results suggested that IGF2BP2 served as an oncogene.…”

IGF2BP2 Promotes Liver Cancer Growth Through an m6A-FEN1-Dependent Mechanism

“…It is regulated by m6A modification enzymes (methyltransferases and demethylases) in a dynamically reversible manner (5,6). In addition, there are also m6A-binding proteins, which can specifically bind to m6A and mediate their biological functions (7,8). In recent years, m6A has been found to be associated with malignant tumors by more and more studies (9,10).…”