Genomic and transcriptomic alterations in m6A regulatory genes are associated with tumorigenesis and poor prognosis in head and neck squamous cell carcinoma.

Genetic alterations in N6-methyladenosine (m6A) regulatory genes are observed in many cancers. Recent studies have shown that newly identified m6A regulatory gene family (IGF2BPs; IGF2BP1, IGF2BP2, and IGF2BP3) were highly expressed in various types of cancer that stabilize and promote translation of multiple oncogenes, resulting in tumor development, survival and drug resistance. However, the oncogenic roles and prognostic values of IGF2BPs in head and neck squamous cell carcinoma (HNSCC) remain largely unknown. In this study, we examined the m6A regulatory genes alteration, their mRNAs expression and the prognostic values in HNSCC. We also analyzed the interaction network and functional enrichment of m6A regulators. Our results showed that m6A regulatory genes were altered in 41% (205/504) of HNSCC patients, of which IGF2BP2 was amplified in 20% (101/504) of HNSCC patents and positively correlated with its mRNA expression. Importantly, we have validated the expression of IGF2BP2 in HNSCC and normal tissue samples. Interestingly, we also found that the IGF2BP2 was frequently co-amplified with the most common oncogenes in HNSCC patients. In addition, this study found that other m6A regulatory genes such as METTL3, METTL14, WTAP, KIAA1429, ZC3H13, RBM15, ALKBH5, FTO, YTHDF1, YTHDF2, YTHDF3, YTHDC1, IGF2BP1, and IGF2BP3 were significantly upregulated in HNSCC samples. Moreover, patients with high expression of IGF2BP1, IGF2BP2, and IGF2BP3 had poor overall survival (OS) than those with low expression. Therefore, it is evident that IGF2BP family plays a key role in the oncogenesis of HNSCC and might serve as novel prognostic biomarkers and potential therapeutic targets in HNSCC. AJCR