A Signature of N6-methyladenosine Regulator-Related Genes Predicts Prognoses and Immune Responses for Head and Neck Squamous Cell Carcinoma

Abstract

This study aimed to construct a signature of N6-methyladenosine (m6A) regulator-related genes that could be used for the prognosis of head and neck squamous cell carcinoma (HNSCC) and to clarify the molecular and immune characteristics and benefits of immune checkpoint inhibitor (ICI) therapy using the prognostic signature to define the subgroups of HNSCC. This study showed that eighteen m6A regulators were abnormally expressed in the Cancer Genome Atlas (TCGA) HNSCC tissues compared with those in normal tissues. We constructed a signature of 12 m6A regulator-related genes using the Cox risk model, combined with the least absolute shrinkage and selection operator (Lasso) variable screening algorithm. Based on the median of the signature risk score, the patients were divided into high- and low-risk groups. The Kaplan–Meier survival analyses showed that patients with high-risk scores demonstrated poorer overall survival (OS) than those with low-risk scores based on TCGA-HNSCC data (p <0.001). The OS of high-risk patients was significantly worse than that of low-risk patients in the GSE65858 (p <0.001) and International Cancer Genome Consortium (ICGC) oral cancer cohorts (p = 0.0089). Furthermore, immune infiltration analyses showed that 8 types of immune cell infiltration showed highly significant differences between the two risk groups (p <0.001). In the Imvigor210CoreBiologies dataset of patients who received ICIs, the objective response rate (ORR) of the low-risk group (32%) was significantly higher than that of the high-risk group (13%). Additionally, patients in the high-risk group presented with a more significant adverse OS than that of the low-risk group (p = 0.00032). GSE78220 also showed that the ORR of the low-risk group (64%) was higher than that of the high-risk group (43%) and the OS of low-risk patients was better than that of high-risk patients (p = 0.0064). The constructed prognostic signature, based on m6A regulator-related genes, could be used to effectively distinguish between prognoses for HNSCC patients. The prognostic signature was found to be related to the immune cell infiltration of HNSCC; it might help predict the responses and prognoses of ICIs during treatment.

Unveiling Anoikis‐related genes: A breakthrough in the prognosis of bladder cancer

“…At the same time, we also predicted the immune response and score using Tumor Immune Dysfunction and Exclusion (TIDE) online tools (http://tide.dfci.harvard.edu) and the IMvigor210CoreBiologies R package. 26 Correlation analysis between risk scores and expression level of immune checkpoint was performed using the ggcorrplot R package. 27…”

Roles of m6A modification in oral cancer (Review)

“…Furthermore, m 6 A modifications have essential roles during the generation of immune responses ( 112 ). A previous study indicated that, depending on m 6 A regulation-related genes, a prognostic marker may effectively determine the prognosis of HNSCC ( 113 ). This prognostic marker was associated with immune cell infiltration in HNSCC ( 113 ).…”

“…A previous study indicated that, depending on m 6 A regulation-related genes, a prognostic marker may effectively determine the prognosis of HNSCC ( 113 ). This prognostic marker was associated with immune cell infiltration in HNSCC ( 113 ). A recent study suggested that METTL3 expression was increased in OSCC and inhibited CD8 + T-cell activation ( 106 ).…”

An Immunogenic Cell Death-Related Classification Predicts Prognosis and Response to Immunotherapy in Hepatocellular carcinoma

“…Second, we also explored the expression of N6-methyladenine (m6A) related genes between the two groups. The gene related to N6-methyladenine (m6A) was obtained from the previous literature 14 . The "ggpubr" and "ggplot2" R packages were used to perform this study.…”