m6A Modification Patterns With Distinct Immunity, Metabolism, and Stemness Characteristics in Soft Tissue Sarcoma.

Autor:	Huang ZD; Department of Spine and Orthopedic Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.; Department of Stomatology, Southern Medical University, Guangzhou, China., Lin LL; Department of Pathology and Pathophysiology, School of Basic Medicine, Wuhan University, Wuhan, China., Liu ZZ; The Third Clinical School, Hubei University of Medicine, Shiyan, China., Hu C; Department of Spine and Orthopedic Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Gu HY; Department of Spine and Orthopedic Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China., Wei RX; Department of Spine and Orthopedic Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Dec 24; Vol. 12, pp. 765723. Date of Electronic Publication: 2021 Dec 24 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.765723
Abstrakt:	N6-methyladenosine (m6A) RNA methylation has been shown to have prognostic value in cancer. Nonetheless, its potential role regarding immunity, metabolism, and stemness in soft tissue sarcoma (STS) remains unknown. We comprehensively estimated the m6A modification patterns and corresponding immunity, metabolism, and stemness characteristics based on 568 STS samples and 21 m6A regulators. The m6Ascore was constructed to quantify m6A modification patterns in individuals using machine learning algorithms. Two distinct m6A modification patterns among the STS patients were identified, which exhibited differences in prognosis, immune cell infiltration, metabolic pathways, stemness, somatic mutation, and copy number variation. Thereafter, immunity-, metabolism-, and stemness phenotype-related genes associated with m6A modification were identified. Furthermore, patients with lower m6Ascores had increased antitumor immune responses, survival benefit under immunotherapy, tumor mutation burden, immunogenicity, and response to anti-PD-1/L1 immunotherapy. Immunotherapy sensitivity was validated using the IMvigor210 dataset. STS patients with lower m6Ascore might be more sensitive to docetaxel and gemcitabine. Finally, pan-cancer analysis illustrated the significant correlations of m6Ascore with clinical outcomes, immune cell infiltration, metabolism, and stemness. This study revealed that m6A modification plays an important role in immunity, metabolism, and stemness in STS. Evaluating the m6A modification pattern and development of m6Ascore may help to guide more effective immunotherapy and chemotherapy strategies. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Huang, Lin, Liu, Hu, Gu and Wei.)
Databáze:	MEDLINE
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