In:
Frontiers in Genetics, Frontiers Media SA, Vol. 13 ( 2022-10-17)
Abstract:
Background: Recent studies demonstrate that N6-methyladenosine (m 6 A) methylation plays a crucial role in colorectal cancer (CRC). Therefore, we conducted a comprehensive analysis to assess the m 6 A modification patterns and identify m 6 A-modified genes in patients with CRC recurrence. Methods: The m 6 A modification patterns were comprehensively evaluated by the NMF algorithm based on the levels of 27 m 6 A 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 m 6 A scoring scheme was used to explore the m 6 A modification patterns of individual tumors with immune responses. The weighted correlation network analysis and univariable and multivariable Cox regression analyses were applied to identify m 6 A-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 m 6 A modification patterns with significant recurrence-free survival (RFS) were identified in 804 CRC patients. The TME characterization revealed that the m 6 A modification pattern with longer RFS exhibited robust immune responses. CRC patients were divided into high- and low-score subgroups according to the m 6 A score individually, which was obtained from the m 6 A-related signature genes. The patients with low m 6 A scores had both longer RFS and overall survival (OS) with altered immune cell infiltration. Notably, m 6 A-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 m 6 A 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 m 6 A-modified genes associated with CRC recurrence, thereby serving as a promising predictive biomarker or therapeutic target for patients with CRC recurrence.
Type of Medium:
Online Resource
ISSN:
1664-8021
DOI:
10.3389/fgene.2022.1043297
DOI:
10.3389/fgene.2022.1043297.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606823-0
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