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

Zi-Yi Feng; Hao-Yu Gao; Tian-Da Feng

doi:10.3389/fcell.2021.672248

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

Front Cell Dev Biol. 2021 Jun 4:9:672248. doi: 10.3389/fcell.2021.672248. eCollection 2021.

Authors

Zi-Yi Feng¹, Hao-Yu Gao², Tian-Da Feng³

Affiliations

¹ Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, China.
² Department of Students, The First Hospital of China Medical University, Shenyang, China.
³ Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.

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.

Keywords: HNSCC; PD-L1; biomarker; lncRNA; m6A regulators; survival analysis; tumor microenvironment.