M6A modification patterns are associated with copy number burden and tumor immune landscape in thyroid cancer

Abstract

BackgroundThe association involving N6-methyladenosine (m6A) modification, molecular subtype and specific immune cell group in tumor microenvironment has been the focus of recent studies. The underlying function of m6A modification in thyroid cancer (TC) remains elusive.MethodsThe m6A modification regulations, molecular character and tumor immune profile of 461 TC patients were explored and then the correlation between them were comprehensively evaluated. The m6Ascore was established using principal component analysis (PCA) to quantify the m6A pattern of individual TC patients. The prognostic significance of the m6Ascore was evaluated by multivariate Cox regression analysis.ResultsFour m6Aclusters (mc1, 2, 3, 4)—characterized by differences in extent of aneuploidy, expression of immunomodulatory genes, mRNA or lncRNA expression pattern and prognosis were identified. T Preliminary validation of m6Ascore was a potential independent prognostic factor of TC involving in mc3. Finally, the prognostic value of the m6Ascore and its association with copy number variation (CNV) and tumor immune microenvironment (TIME) of TC in mc3 were verified.ConclusionsThe correlation between m6A modification, the copy number burden and tumor immune landscape in TC was demonstrated. A m6Acluster-mc3 with low m6Ascore and high CNV molecular subtype was identified with poor clinical prognosis, low infiltrating immunocyte and weak effector T cell. A three-gene clinical prognosis model for TC based on 4 m6a cluster expression was established. Understanding of TIME is enhanced by comprehensive assessment of m6A patterns in individual TC patients and gives a new insight toward improved immunotherapy strategies for TC cancer patients.