4.7 Article

Integrated analyses of m1A regulator-mediated modification patterns in tumor microenvironment-infiltrating immune cells in colon cancer

Journal

ONCOIMMUNOLOGY
Volume 10, Issue 1, Pages -

Publisher

TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2021.1936758

Keywords

m(1)A; tumor microenvironment; immunotherapy; colon cancer

Funding

  1. Natural Science Foundation of China [81972012]
  2. Medical and Health Science and Technology project of Zhejiang Province [2017KY418]

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The study highlights the crucial role and potential impact of m(1)A modification patterns in the tumor microenvironment, particularly in influencing the prognosis of colon cancer patients and immune cell infiltration. The analysis of m(1)A score plays a significant role in understanding the complexities and diversity of the immune response in the context of cancer.
Emerging evidence has revealed the crucial role of transcriptional RNA methyladenosine modification in immune response. However, the potential role of RNA N1-methyladenosine (m(1)A) modification of immune cells in the tumor microenvironment (TME) still remains unclear. In this study, we identified three distinct m(1)A modification patterns based on the integrated analyses of nine m(1)A regulators, which are significantly related to Relapse-free survival (RFS), Overall survival (OS), and TME infiltration cells in colon cancer patients. Furthermore, the m1AScore was generated by using principal components analysis (PCA) of expression of the 71 m(1)A-related genes to further demonstrate the characteristics of m(1)A patterns in colon cancer. In summary, a low m1AScore could be characterized by lower EMT, pan-F TBRS, and TNM stages, as well as less presence of lymphatic invasion, and, hence, good prognosis. At the same time, a low m1AScore could also be linked to CD8 + T effector proliferation, in addition to high microsatellite instability (MSI), neoantigen burden and PD-L1 expression, showing prolonged survival and better response after undergoing an anti-PD-L1 immunotherapy regimen in the public immunotherapy cohort. Our work reveals that m(1)A modification patterns play a key role in the formation of TME complexity and diversity in the context of immune cell infiltration. Accordingly, this m1AScore system provides an efficient method by which to identify and characterize TME immune cell infiltration, thereby allowing for more personalized and effective antitumor immunotherapy strategies.

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