Frontiers in Genetics (Oct 2022)
Identification of genes modified by N6-methyladenosine in patients with colorectal cancer recurrence
- Qianru Zhu,
- Qianru Zhu,
- Qianru Zhu,
- Qianru Zhu,
- Xingxing Huang,
- Xingxing Huang,
- Xingxing Huang,
- Xingxing Huang,
- Shuxian Yu,
- Shuxian Yu,
- Shuxian Yu,
- Lan Shou,
- Lan Shou,
- Lan Shou,
- Ruonan Zhang,
- Ruonan Zhang,
- Ruonan Zhang,
- Ruonan Zhang,
- Han Xie,
- Han Xie,
- Han Xie,
- Zimao Liang,
- Zimao Liang,
- Zimao Liang,
- Zimao Liang,
- Xueni Sun,
- Xueni Sun,
- Xueni Sun,
- Jiao Feng,
- Jiao Feng,
- Jiao Feng,
- Ting Duan,
- Ting Duan,
- Ting Duan,
- Mingming Zhang,
- Mingming Zhang,
- Mingming Zhang,
- Yu Xiang,
- Yu Xiang,
- Yu Xiang,
- Xinbing Sui,
- Xinbing Sui,
- Xinbing Sui,
- Xinbing Sui,
- Xinbing Sui,
- Xinbing Sui,
- Weiwei Jin,
- Weiwei Jin,
- Lili Yu,
- Qibiao Wu,
- Qibiao Wu,
- Qibiao Wu,
- Qibiao Wu
Affiliations
- Qianru Zhu
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China
- Qianru Zhu
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Qianru Zhu
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Qianru Zhu
- 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
- Xingxing Huang
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China
- Xingxing Huang
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Xingxing Huang
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Xingxing Huang
- 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
- Shuxian Yu
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Shuxian Yu
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Shuxian Yu
- 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
- Lan Shou
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Lan Shou
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Lan Shou
- 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
- Ruonan Zhang
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China
- Ruonan Zhang
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Ruonan Zhang
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Ruonan Zhang
- 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
- Han Xie
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China
- Han Xie
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Han Xie
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Zimao Liang
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China
- Zimao Liang
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Zimao Liang
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Zimao Liang
- 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
- Xueni Sun
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Xueni Sun
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Xueni Sun
- 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
- Jiao Feng
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Jiao Feng
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Jiao Feng
- 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
- Ting Duan
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Ting Duan
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Ting Duan
- 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
- Mingming Zhang
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Mingming Zhang
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Mingming Zhang
- 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
- Yu Xiang
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Yu Xiang
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Yu Xiang
- 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
- Xinbing Sui
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China
- Xinbing Sui
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Xinbing Sui
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Xinbing Sui
- 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
- Xinbing Sui
- Zhuhai MUST Science and Technology Research Institute, Zhuhai, Guangdong, China
- Xinbing Sui
- Department of Gastrointestinal-Pancreatic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
- Weiwei Jin
- Department of Gastrointestinal-Pancreatic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China
- Weiwei Jin
- Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, Zhejiang, China
- Lili Yu
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China
- Qibiao Wu
- State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, China
- Qibiao Wu
- School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, China
- Qibiao Wu
- Guangdong-Hong Kong-Macao Joint Laboratory for Contaminants Exposure and Health, Guangdong University of Technology, Guangzhou, Guangdong, China
- Qibiao Wu
- Zhuhai MUST Science and Technology Research Institute, Zhuhai, Guangdong, China
- DOI
- https://doi.org/10.3389/fgene.2022.1043297
- Journal volume & issue
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Vol. 13
Abstract
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.
Keywords
- colorectal cancer
- m6A methylation modification
- tumor immune microenvironment
- recurrence
- overall survival
