Links Between N6-Methyladenosine and Tumor Microenvironments in Colorectal Cancer

Frontiers in Cell and Developmental Biology

Ke Zhang¹  Qin Li²  Song Li³  Qingchang Jin⁴  Lajie Man⁴  Haoming Gong⁴  Lin Zhang⁵  Yundi Zhang⁶ 

[1] Department of General Practice, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China;Department of General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China;Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China;Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China;Department of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China;National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;

关键词: colorectal cancer;    immunotherapy;    N6-methyladenosine;    tumor microenvironments;    molecular classification;   

DOI  :  10.3389/fcell.2022.807129

来源: DOAJ

【 摘 要 】

N6-methyladenosine (m6A) is a critical epigenetic modification for tumor malignancies, but its role in regulating the tumor microenvironments (TMEs) has not been fully studied. By integrating multiple data sets and multi-omics data, we comprehensively evaluated the m6A “writers,” “erasers,” and “readers” in colorectal cancer and their association with TME characteristics. The m6A regulator genes showed specific patterns in co-mutation, copy number variation, and expression. Based on the transcriptomic data of the m6A regulators and their correlated genes, two types of subtyping systems, m6AregCluster and m6AsigCluster, were developed. The clusters were distinct in pathways (metabolism/inflammation/extracellular matrix and interaction), immune phenotypes (immune-excluded/immune-inflamed/immune-suppressive), TME cell composition (lack immune and stromal cells/activated immune cells/stromal and immune-suppressive cells), stroma activities, and survival outcomes. We also established an m6Ascore associated with molecular subgroups, microsatellite instability, DNA repair status, mutation burdens, and survival and predicted immunotherapy outcomes. In conclusion, our work revealed a close association between m6A modification and TME formation. Evaluating m6A in cancer has helped us comprehend the TME status, and targeting m6A in tumor cells might help modulate the TME and improve tumor therapy and immunotherapy.

【 授权许可】

Unknown