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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is a commonly occurring malignancy reported in humans worldwide [1, 2]
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
544 cases based on the Cancer Genome Atlas (TCGA)-HNSCC transcriptomic data were analyzed, including 500 tumor tissues and 44 normal tissue samples, revealing that the expression of 18 m6A regulator genes was higher in tumor tissues than that in normal tissues, including 7 m6A writer genes (VIRMA, RBM15, METTL3, Wilms tumor 1-associated protein (WTAP), CBLL1, METTL14, and LRPPRC), 9 reader genes (IGF2BP1, heterogeneous nuclear ribonucleoprotein C (HNRNPC), HNRNPA2B1, YTHDF1, ELAVL1, FMR1, YTHDF3, YTHDF2, and YTH domain-containing 1 (YTHDC1)) and 2 erasers genes (ALKBH5 and fat mass- and obesityassociated protein (FTO)) (Figures 2A, B)
Summary
Head and neck squamous cell carcinoma (HNSCC) is a commonly occurring malignancy reported in humans worldwide [1, 2]. The current standard management for HNSCC includes the assessment of patients’ prognoses based on the size, location, and invasion of their tumors using the Tumor, Nodes, and Metastases (TNM) classification system; strategies are formulated on this basis [5]. Patients within the same TNM stage continue to demonstrate different responses to treatment [6]. It is imperative to discover stable and reliable molecular signatures to evaluate the prognoses of patients and to propose more effective treatments. M6A methylation plays an essential role in many physiological and pathological processes, including immune response generation, microRNA editing, and the progression of various cancers [12,13,14]
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