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Published on: August 23, 2019
Characterization of m6A methylation modifications and tumor microenvironment infiltration in thyroid cancer
Fei-Hong Ji1, Zhen Yang1, Chenyu Sun2
1Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Background:
Thyroid cancer (TC) is the most common endocrine malignancy worldwide, and immunotherapy is a new cancer treatment that stimulates and enhances the natural ability of the immune system to fight cancer cells. The role of RNA N6-methyladenosine (m6A) related genes in these challenges has recently become a research hotspot, but he potential role of m6A modifications in tumor microenvironment (TME) cell infiltration remains unknown.
Purpose:
There is growing evidence that m6A plays a critical role in the regulation of gene expression by participating in important biological processes. A comprehensive analysis of the m6A regulator-mediated infiltration characteristics of the TME will help advance the understanding of immune regulation in thyroid tumors.
Methods:
This study assessed m6A modification modes in 510 thyroid cancer samples from the Cancer Genome Atlas (TCGA) databases according to a comprehensive set of 24 m6A regulators. In this study, we analyzed the biological characteristics and m6A methylation modification patterns. Based on this, we constructed m6A signatures and analyzed m6A modification features in tumor somatic mutations and TCGA molecular subtypes.
Results:
These modification modes were systematically linked to TME cell infiltration signatures. m6A modification patterns were comprehensively assessed and correlated with immune cell infiltration features in the TME. An unsupervised clustering approach was applied and three distinct m6A modification subtypes and three m6A-associated gene subtypes were identified. Additionally, three distinct m6A methylation modification modes were identified in the thyroid cancer samples. The TME profiles of the identified genetic subtypes were strongly congruent with the immuno-heat and immuno-cold phenotypes.
Conclusions:
The results revealed that m6A modifications play an integral role in the diversity and complexity of thyroid carcinomas. Evaluating the m6A modification patterns of individual tumors will create more efficient immunotherapeutic strategies. A comprehensive analysis of the role of TME in thyroid cancer provides a research idea for studying the effect of m6A epigenetics on thyroid tumors and their immune microenvironment.
Insights
RNA N6-methyladenosine (m6A) modifications significantly impact thyroid cancer complexity and immune cell infiltration. Understanding these m6A patterns can lead to more effective immunotherapies for thyroid tumors.
Area of Science:
- Oncology
- Immunology
- Epigenetics
Background:
- Thyroid cancer (TC) is a prevalent endocrine malignancy.
- Immunotherapy enhances the immune system's ability to combat cancer.
- The role of RNA N6-methyladenosine (m6A) genes in TC and tumor microenvironment (TME) cell infiltration is under investigation.
Purpose of the Study:
- To comprehensively analyze m6A regulator-mediated TME cell infiltration characteristics in thyroid cancer.
- To advance the understanding of immune regulation in thyroid tumors through m6A modification analysis.
Main Methods:
- Assessed m6A modification modes in 510 TCGA thyroid cancer samples using 24 m6A regulators.
- Analyzed biological characteristics, m6A methylation patterns, and constructed m6A signatures.
- Examined m6A modification features in tumor somatic mutations and TCGA molecular subtypes.
Main Results:
- Linked m6A modification modes to TME cell infiltration signatures.
- Identified three distinct m6A modification subtypes and three m6A-associated gene subtypes.
- Correlated TME profiles of genetic subtypes with immuno-heat and immuno-cold phenotypes.
Conclusions:
- m6A modifications are integral to the diversity and complexity of thyroid carcinomas.
- Evaluating individual tumor m6A modification patterns can optimize immunotherapeutic strategies.
- This study provides insights into m6A epigenetics in thyroid cancer and its immune microenvironment.
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