AUTHOR=Wang Enhao , Li Yang , Ming Ruijie , Wei Jiahui , Du Peiyu , Zhou Peng , Zong Shimin , Xiao Hongjun 

TITLE=The Prognostic Value and Immune Landscapes of a m6A/m5C/m1A-Related LncRNAs Signature in Head and Neck Squamous Cell Carcinoma

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.718974

DOI=10.3389/fcell.2021.718974

ISSN=2296-634X

ABSTRACT=<p><bold>Background:</bold> N6-methyladenosine (m<sup>6</sup>A), 5-methylcytosine (m<sup>5</sup>C) and N1-methyladenosine (m<sup>1</sup>A) are the main RNA methylation modifications involved in the progression of cancer. However, it is still unclear whether m<sup>6</sup>A/m<sup>5</sup>C/m<sup>1</sup>A-related long non-coding RNAs (lncRNAs) affect the prognosis of head and neck squamous cell carcinoma (HNSCC).</p><p><bold>Methods:</bold> We summarized 52 m<sup>6</sup>A/m<sup>5</sup>C/m<sup>1</sup>A-related genes, downloaded 44 normal samples and 501 HNSCC tumor samples with RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) database, and then searched for m<sup>6</sup>A/m<sup>5</sup>C/m<sup>1</sup>A-related genes co-expressed lncRNAs. We adopt the least absolute shrinkage and selection operator (LASSO) Cox regression to obtain m<sup>6</sup>A/m<sup>5</sup>C/m<sup>1</sup>A-related lncRNAs to construct a prognostic signature of HNSCC.</p><p><bold>Results:</bold> This prognostic signature is based on six m<sup>6</sup>A/m<sup>5</sup>C/m<sup>1</sup>A-related lncRNAs (AL035587.1, AC009121.3, AF131215.5, FMR1-IT1, AC106820.5, PTOV1-AS2). It was found that the high-risk subgroup has worse overall survival (OS) than the low-risk subgroup. Moreover, the results showed that most immune checkpoint genes were significantly different between the two risk groups (<italic>p</italic> &lt; 0.05). Immunity microenvironment analysis showed that the contents of NK cell resting, macrophages M2, and neutrophils in samples of low-risk group were significantly lower than those of high-risk group (<italic>p</italic> &lt; 0.05), while the contents of B cells navie, plasma cells, and T cells regulatory (Tregs) were on the contrary (<italic>p</italic> &lt; 0.05). In addition, patients with high tumor mutational burden (TMB) had the worse overall survival than those with low tumor mutational burden.</p><p><bold>Conclusion:</bold> Our study elucidated how m<sup>6</sup>A/m<sup>5</sup>C/m<sup>1</sup>A-related lncRNAs are related to the prognosis, immune microenvironment, and TMB of HNSCC. In the future, these m<sup>6</sup>A/m<sup>5</sup>C/m<sup>1</sup>A-related lncRNAs may become a new choice for immunotherapy of HNSCC.</p>