Abstract
N6-methyladenosine (m6A) plays crucial roles in a diverse range of physiological and pathological processes, and it is believed that it tremendously promotes neoplasia and progression. However, knowledge of the molecular characteristics of m6A modification, its prognostic value, and the infiltration of immune cell populations in head and neck squamous cell carcinoma (HNSCC) is still insufficient. Therefore, a pan-cancer genomic analysis was systematically performed here by examining m6A regulators at the molecular level within 33 multiple cancer types, and the correlations between the expression of m6A molecules were researched using datasets from The Cancer Genome Atlas (TCGA). Based on the above analysis, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is upregulated in HNSCC and may serve as an independent prognostic factor of overall survival, thus showing potential as a prognostic biomarker in HNSCC. Genetic alteration analyses elucidated the reasons for the abnormal upregulation of IGF2BP2 in HNSCC. As a result, IGF2BP2 was selected for further univariate and multivariate analyses. The functions of the related genes were annotated through gene set enrichment analysis, and the activation states of multiple biological pathways were shown by gene set variation analysis. We found that LRRC59 and STIP1 may act as IGF2BP2-associated genes to have a regulatory function in the m6A modification. In addition, we found that the status of immune cell infiltration was correlated with the level of IGF2BP2 gene expression. Our results provide supplementation at the molecular level for epigenetic regulation in HNSCC and insight into effective immunotherapy targets and strategies.
Highlights
The classic epigenetic modifications are DNA methylation, histone modification, and chromatin remodeling, which take part in many basic biological activities of carcinogenesis, including malignant development, and are associated with the prognosis of various kinds of cancer, including head and neck squamous cell carcinoma (HNSC, HNSCC) [1]
The TIMER database was used for analysis, and we found that m6A regulators were abnormally expressed in cancers in a cancer-specific pattern
The GSCALite web server was used, and we found twenty-four m6A regulators to be differentially expressed in 14 cancer types (Figure 1E)
Summary
The classic epigenetic modifications are DNA methylation, histone modification, and chromatin remodeling, which take part in many basic biological activities of carcinogenesis, including malignant development, and are associated with the prognosis of various kinds of cancer, including head and neck squamous cell carcinoma (HNSC, HNSCC) [1]. Reports on tumor methylation modifications have concentrated mostly on DNA methylation and offered potential biomarkers for cancer diagnosis [2]. In addition to these traditional epigenetic modifications, mRNA modification is known as another epigenetic regulation of gene expression. Its dynamic regulation and disorder are closely related to translation control, RNA splicing defects, and the occurrence, maintenance, and progression of various tumors [3, 4]. Among the types of RNA modifications, N6-methyladenosine (m6A) is recognized as the first and most common modification in eukaryotic mRNA [6]
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