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Identification of genes modified by N6-methyladenosine in patients with colorectal cancer recurrence

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机构： [1]State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China. [2]School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China. [3]Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China. [4]Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, China. [5]Zhuhai MUST Science and Technology Research Institute, Zhuhai, Guangdong, China. [6]Department of Gastrointestinal-Pancreatic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China. [7]Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang, China.

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关键词： colorectal cancer m6A methylation modification tumor immune microenvironment recurrence overall survival

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Background: Recent studies demonstrate that N6-methyladenosine (m6A) methylation plays a crucial role in colorectal cancer (CRC). Therefore, we conducted a comprehensive analysis to assess the m6A modification patterns and identify m6A-modified genes in patients with CRC recurrence. Methods: The m6A modification patterns were comprehensively evaluated by the NMF algorithm based on the levels of 27 m6A regulators, and tumor microenvironment (TME) cell-infiltrating characteristics of these modification patterns were systematically assessed by ssGSEA and CIBERSORT algorithms. The principal component analysis algorithm based on the m6A scoring scheme was used to explore the m6A modification patterns of individual tumors with immune responses. The weighted correlation network analysis and univariable and multivariable Cox regression analyses were applied to identify m6A-modified gene signatures. The single-cell expression dataset of CRC samples was used to explore the tumor microenvironment affected by these signatures. Results: Three distinct m6A modification patterns with significant recurrence-free survival (RFS) were identified in 804 CRC patients. The TME characterization revealed that the m6A modification pattern with longer RFS exhibited robust immune responses. CRC patients were divided into high- and low-score subgroups according to the m6A score individually, which was obtained from the m6A-related signature genes. The patients with low m6A scores had both longer RFS and overall survival (OS) with altered immune cell infiltration. Notably, m6A-modified genes showed significant differences related to the prognosis of CRC patients in the meta-GEO cohort and TCGA cohort. Single-cell expression indicated that ALVRL1 was centrally distributed in endothelial tip cells and stromal cells. Conclusion: The m6A modification plays an indispensable role in the formation of TME diversity and complexity. Importantly, the signatures (TOP2A, LRRC58, HAUS6, SMC4, ACVRL1, and KPNB1) were identified as m6A-modified genes associated with CRC recurrence, thereby serving as a promising predictive biomarker or therapeutic target for patients with CRC recurrence.Copyright © 2022 Zhu, Huang, Yu, Shou, Zhang, Xie, Liang, Sun, Feng, Duan, Zhang, Xiang, Sui, Jin, Yu and Wu.

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出版当年[2021]版：

大类 | 3 区生物学

小类 | 3 区遗传学

最新[2025]版：

大类 | 3 区生物学

小类 | 3 区遗传学

第一作者：

第一作者机构： [1]State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China. [2]School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China. [3]Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China. [4]Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, China.

通讯作者：

通讯机构： [1]State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China. [2]School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China. [3]Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China. [5]Zhuhai MUST Science and Technology Research Institute, Zhuhai, Guangdong, China. [6]Department of Gastrointestinal-Pancreatic Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China. [7]Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang, China.

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Identification of genes modified by N6-methyladenosine in patients with colorectal cancer recurrence

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