IGF2BP2 serves as a core m6A regulator in head and neck squamous cell carcinoma.

Abstract

Methylation of N6 adenosine (m6A) plays a crucial role in the development and progression of cancers. Its modification is regulated by three types of m6A-related regulators (methyltransferases (writers), demethylases (erasers), and RNA-binding proteins (readers)). Till now, the functions and roles of these regulators in head and neck squamous cell carcinoma (HNSC) remain largely unexplored. Therefore, we utilized the open HNSC dataset in The Cancer Genome Atlas (TCGA), four different cell lines, and our HNSC patient samples (n=40) to explore the clinical significance of 19 m6A regulators, and selected the most significant prognosis-related regulator. Authentic analyses based on online websites were also used in the study (Oncomine, UALCAN, Kaplan-Meier plotter, Human Protein Atlas (HPA), cBioPortal, LinkedOmics, String, etc.). From the results, general overexpression of m6A regulators was observed in pan-cancer, especially in HNSC. IGF2BP2 was recognized as the hub m6A regulator, which was an independent, unfavorable prognostic factor in HNSC. Its mRNA and protein expression in HNSC were significantly up-regulated. Gene mutation types of IGF2BP2 in HNSC (32%) were mainly mRNA High or Amplification, which represented the high expression of IGF2BP2. And these mutations were associated with a poor prognosis. In functional analysis, IGF2BP2 was negatively correlated to tumor immune infiltration in HNSC. Finally, HMGA2 might interact with the IGF2BP2 in HNSC. In conclusion, IGF2BP2 serves as a core m6A regulator among all regulators in HNSC, which has a high expression and predicts the poor prognosis of HNSC patients independently. IGF2BP2 might bring a new direction for HNSC treatment in the future.