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Comprehensive analysis of m6A regulator-based methylation modification patterns characterized by distinct immune profiles in colon adenocarcinomas

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单位: [1]Shanxi Med Univ, Tongji Shanxi Hosp, Shanxi Bethune Hosp, Dept Gen Surg,Shanxi Acad Med Sci,Hosp 3, Taiyuan, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Wuhan, Peoples R China [3]Shanxi Med Univ, Taiyuan, Peoples R China [4]Licheng Peoples Hosp, Dept Gen Surg, Changzhi, Peoples R China [5]Shanxi Prov Canc Hosp, Dept Breast Surg, Taiyuan, Peoples R China
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关键词: Colon adenocarcinoma M(6)A modification Tumor microenvironment Immunotherapy

摘要:
Mounting evidences have indicated that RNA N-6-methyladenosine (m(6)A) modification played important roles in tumor formation and growth. However, it is rarely reported that m(6)A modifications are involved in the immune regulation and tumor microenvironment (TME) formation. In this study, we aimed to investigate the correlation between m(6)A modifications and TME regulation of colon adenocarcinoma (COAD) by bioinformatic analysis. NMF algorithm was applied to carry out consensus molecular subtype analysis on 36 selected m(6)A regulators regarding methylation modification, to identify m(6)A modification patterns and characteristics of m(6)A related genes in colon adenocarcinoma (COAD). Further, the relative infiltration levels of different immune cell subsets were quantified by ssGSEA and CIBERSORT algorithms, and a m(6)Sig scoring scheme was constructed to predict the prognosis and evaluate the response to immunotherapy in the patients with COAD. Among 579 COAD samples, we identified three different m(6)A modification patterns which were related to different biological pathways and clinical outcomes. Then, a scoring scheme termed "m(6)Sig score" was developed based on m(6)A-related characteristic genes, and was utilized to score patients with COAD into groups. We found that COAD patients with lower m(6)Sig scores exhibited prolonged survival and potentiated immune infiltration, which were associated with higher tumor mutation load, lower PD-L1 expression, and higher mutation rates of SMG (such as TTN and KRAS). Moreover, analysis regarding evaluation of immune response revealed that the patients with lower m(6)Sig scores had higher Immunophenoscore. Collectively, our study provided in depth insight into the interactions between m(6)A modification and regulation of TME. In addition, the quantitative evaluation of m(6)A modification patterns in our results may have implications in further immunotherapy for individual COAD patients.

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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
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出版当年[2020]版:
Q2 GENETICS & HEREDITY
最新[2023]版:
Q2 GENETICS & HEREDITY

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第一作者单位: [1]Shanxi Med Univ, Tongji Shanxi Hosp, Shanxi Bethune Hosp, Dept Gen Surg,Shanxi Acad Med Sci,Hosp 3, Taiyuan, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Wuhan, Peoples R China
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通讯机构: [1]Shanxi Med Univ, Tongji Shanxi Hosp, Shanxi Bethune Hosp, Dept Gen Surg,Shanxi Acad Med Sci,Hosp 3, Taiyuan, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Wuhan, Peoples R China [5]Shanxi Prov Canc Hosp, Dept Breast Surg, Taiyuan, Peoples R China
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