Immune Infiltrates of m6A RNA Methylation-Related lncRNAs and Identification of PD-L1 in Patients With Primary Head and Neck Squamous Cell Carcinoma

Abstract

Background: The purpose of this study was to determine the association between m6A-modified lncRNAs, immune infiltration, and PD-L1 expression in patients with primary head and neck squamous cell carcinoma (HNSCC) and the prognostic value of m6A RNA methylation-related lncRNAs in HNSCC.Methods: We downloaded the RNA-seq transcriptome data and the clinical information for HNSCC from the TCGA databases and used consensus clustering analysis to divide the samples into two groups. To identify a risk signature, least absolute shrinkage and selection operator (LASSO) analyses were conducted. the association between m6A-modified lncRNAs, immune infiltration, and PD-L1 expression were detected by using the R packages. What is more, we used cBioPortal tools to identify genomic alterations and PD-L1 mutations and Gene set enrichment analysis (GSEA) was utilized to predict downstream access of two clusters.Results: Notably, lncRNAs play significant roles in tumorigenesis and development. In total, we identified two subtypes of HNSCC according to consensus clustering of the m6A RNA methylation-related lncRNAs, and the T, grade and age were proven to be related to the subtypes. The Cox regression and LASSO analyses identified a risk signature including GRHL3-AS1, AL121845.4, AC116914.2, AL513190.1. The prognostic value of the risk signature was then proven. The selected gene PD-L1 mutations and the immune infiltration in both groups were further explored.Conclusion: Collectively, our study elucidated the important role of m6A RNA methylation- related lncRNAs in tumor microenvironment of HNSCC. The proposed m6A RNA methylation- related lncRNAs might serve as crucial mediators of tumor microenvironment of HNSCC, representing promising therapeutic targets in improving immunotherapeutic efficacy.

Identification and Validation of the Pyroptosis-Related Molecular Subtypes of Lung Adenocarcinoma by Bioinformatics and Machine Learning

“…A total of 12 N6-methyladenosine (m6A) regulatory genes were selected ( ALKBH5, FTO, HNRNPC, METTL3, METTL14, RBM15, WTAP, YTHDC1, YTHDC2, YTHDF1, YTHDF2 , and ZC3H13 ) as classical regulators of m6A RNA methylation according to previously published studies ( Feng et al, 2021 ; Hou et al, 2021 ; Wang W. et al, 2021 ; Zheng B. et al, 2021 ). We systematically compared the mRNA expression levels of these regulatory genes base on RNA-seq transcriptome data and visualized the analysis results using boxplots.…”

Roles of Major RNA Adenosine Modifications in Head and Neck Squamous Cell Carcinoma

“…Of the expression of many m 6 A regulatory genes, including writers (METTL3, METTL14, WTAP, ZC3H13 and RBM15), erasers (ALKBH5 and FTO), and readers (YTHDF1, YTHDF2, YTHDF3, YTHDC1, IGF2BP1 and IGF2BP3) were found to be significantly increased in HNSCC tissues (Feng et al, 2021;Paramasivam et al, 2021). Deng et al pointed out that the expression of m 6 A methylation regulatory genes is significantly related to the prognosis of HNSCC (Deng et al, 2021).…”

“…The higher the m 6 A-modified lncRNA expression level, the higher the survival rate of HNSCC patients. In other words, these four m 6 A-modified lncRNAs showed protective effects for HNSCC patients ( Feng et al, 2021 ). This finding differs from public opinion, but indicates that the biological role of m 6 A methylation modifications in HNSCC requires further exploration.…”

Construction of Prognostic Risk Model of 5-Methylcytosine-Related Long Non-Coding RNAs and Evaluation of the Characteristics of Tumor-Infiltrating Immune Cells in Breast Cancer

“…RNA modification-related lncRNAs have been confirmed to be associated with head and neck squamous cell carcinoma, colorectal cancer, hepatocellular carcinoma, and liver cancer (Tu et al, 2020;Xue et al, 2020;Zuo et al, 2020;Feng et al, 2021). However, the role of 5-methylcytosine-related lncRNAs (m5C-lncRNAs) in BC cells is still poorly defined.…”