Abstract
Recent studies have shown that RNA N6-methyladenosine (m6A) modification plays an important part in tumorigenesis and immune-related biological processes. However, the comprehensive landscape of immune cell infiltration characteristics in the tumor microenvironment (TME) mediated by m6A methylation modification in pancreatic cancer has not yet been elucidated. Based on consensus clustering algorithm, we identified two m6A modification subtypes and then determined two m6A-related gene subtypes among 434 pancreatic cancer samples. The TME characteristics of the identified gene subtypes were highly consistent with the immune-hot phenotype and the immune-cold phenotype respectively. According to the m6A score extracted from the m6A-related signature genes, patients can be divided into high and low m6A score groups. The low score group displayed a better prognosis and relatively strong immune infiltration. Further analysis showed that low m6A score correlated with lower tumor mutation burden and PD-L1 expression, and indicated a better response to immunotherapy. In general, m6A methylation modification is closely related to the diversity and complexity of immune infiltration in TME. Evaluating the m6A modification pattern and immune infiltration characteristics of individual tumors can help deepen our understanding of the tumor microenvironment landscape and promote a more effective clinical practice of immunotherapy.
Highlights
More than 160 RNA modifications including N7-methylguanine (m7G), N6-methyladenosine (m6A), and N5-methylcytosine (m5C) have been identified
Analysis of copy number variation of 23 m6A regulators showed that copy number variation data (CNV) mutations were common in Pancreatic cancer (PC)
Recent studies have shown that m6A methylation modification plays an indispensable role in a variety of immune-related biological processes, including innate and acquired immune response, immune recognition, immune cell dynamic balance, and anti-tumor immune response [22]
Summary
More than 160 RNA modifications including N7-methylguanine (m7G), N6-methyladenosine (m6A), and N5-methylcytosine (m5C) have been identified. These modifications play a significant role in regulating RNA fate [1]. M6A is regarded as the most important and abundant mRNA modification, accounting for more than 80% of all RNA methylation modifications [2]. Abnormal expression and genetic alterations of m6A regulators are closely related to events such as developmental defects, metabolic disorders, abnormal immune regulation, and tumor progression [10, 11]. A comprehensive understanding of potential m6A regulators’ expression perturbation and genetic variation under cancer heterogeneity will facilitate the identification of therapeutic targets based on RNA methylation [12, 13]
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