Comprehensive Investigation of m6A Regulators for Prognosis in Head and Neck Squamous Cell Carcinoma.

Abstract

The early detection of head and neck squamous cell carcinoma (HNSCC) has an important impact on the clinical prognosis. N6-methyladenosine (m6A) is involved in the post-transcriptional regulation of tumorigenesis and development. In this study, the prognosis and biological functions of m6A regulator targets in HNSCC were explored. RNA-Seq expression data and clinical information from TCGA-HNSCC and GSE23036 datasets were collected. The mRNA levels of IGF2BP2 and IGF2BP3 in tumor tissues were significantly up-regulated. Differential expression and functional enrichment analysis of potential targets for IGF2BP2 and IGF2BP3 obtained from the m6A2Target database showed that they were significantly enriched in cell cycle-related pathways. The Cox regression analysis was performed to establish a three-mRNA signature including PLAU, LPIN1 and AURKA. The prognostic effect was verified in the external dataset GSE41613. Further studies revealed that the three-mRNA signature was significantly associated with survival in the clinical subgroup. The ROC curve, Harrell consistency index and decision curve comparison used to compare the predictive effect of the three-mRNA signature and the other signatures in previous studies showed that the three-mRNA signature had better predictive effect on the prognosis of HNSCC patients. The three-mRNA signature expression were verified in HNSCC cell lines with qRT-PCR and Western blot. Sequence analysis showed that m6A-modification sites existed on PLAU, LPIN1 and AURKA genes. In conclusion, the three-mRNA signature has been proved to be useful on evaluating the prognosis and contributing to the personalized treatment of HNSCC, and IGB2BP2/3 were related to the cell cycle in HNSCC.