m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma

Huang, Xiongpei; Qiu, Zecheng; Li, Liusheng; Chen, Bin; Huang, Peiyuan

doi:10.18632/aging.203456

Cited by 18 publications

(17 citation statements)

References 34 publications

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“…ese processes help to protect tumor cells from clearance, inhibit cell death, and promote proliferation to further aid tumor cell migration and metastasis. Most of the current studies have focused on immunomodulation of tumors [28], focusing on addressing the sustained suppression of adaptive immune responses by TME [29]. Encouragingly, previous studies have demonstrated a strong association between m 6 A methylation and tumor immunotherapy; for example, studies have reported a broad regulatory mechanism of m 6 A on the tumor microenvironment in gastric cancer [25].…”

Section: Discussionmentioning

confidence: 99%

“…A limitation of previous studies on TME may be that they have focused on trends in only a few immune cells. For example, baseline levels of CD4+/CD8+ T cells, macrophage M1, and NK cells, and baseline levels of inflammatory cytokines in tumor invasion have been associated with immune responses [29][30][31]. In contrast, most studies targeting m 6 A modulators in TME have also focused on a single TME cell type (macrophages and CD8 T cells) or a single m 6 A modulator, which has led to the characterization of TME immune cell infiltration mediated by the combined effects of multiple m 6 A modulators not being adequately studied [25].…”

Section: Discussionmentioning

confidence: 99%

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Application of m6A and TME in Predicting the Prognosis and Treatment of Clear Cell Renal Cell Carcinoma

Pei

Wang

et al. 2022

Journal of Oncology

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Background. Previous studies have shown that RNA N6-methyladenosine (m6A) plays an important role in the construction of the tumor microenvironment (TME). However, how m6A plays a role in the TME of clear cell renal cell carcinoma remains unclear. Methods. Based on 23 m6A modulators, we applied consensus cluster analysis to explore the different m6A modification profiles of ccRCC. The CIBERSORT method was employed to reveal the correlation between TME immune cell infiltration and different m6A modification patterns. A m6A score was constructed using a principal component analysis algorithm to assess and quantify the m6A modification patterns of individual tumors. Results. Three distinct m6A modification patterns of ccRCC were identified. The characteristics of TME cell infiltration in these three patterns were consistent with immune rejection phenotype, immune inflammation phenotype, and immune desert phenotype. In particular, when m6A scores were high, TME was characterized by immune cell infiltration and patient survival was higher ( p < 0.05 ). When m6A scores were low, TME was characterized by immunosuppression and patient survival was lower ( p < 0.05 ). The immunotherapy cohort confirmed that patients with higher m6A scores had significant therapeutic advantages and clinical benefits. Conclusions. The m6A modification plays an important role in the formation of TME. The m6A scoring system allows the identification of m6A modification patterns in individual tumors, discriminates the immune infiltrative features of TME, and provides more effective prognostic indicators and treatment strategies for immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Application of m6A and TME in Predicting the Prognosis and Treatment of Clear Cell Renal Cell Carcinoma

Pei

Wang

et al. 2022

Journal of Oncology

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“…Furthermore, m6A modification is greatly affected by the expression and function of these regulatory proteins, and studying these regulatory proteins can enhance understanding of the role of m6A in gene regulation ( Chong et al, 2021 ). It has also been observed that m6A modification under the influence of regulatory factors is associated with inflammation, the tumor microenvironment (TME), and immune response ( Huang et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

m6A Regulator-Mediated RNA Methylation Modification Patterns Regulate the Immune Microenvironment in Osteoarthritis

Duan

Yan

et al. 2022

Front. Genet.

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Epigenetic regulation, particularly RNA n6 methyl adenosine (m6A) modification, plays an important role in the immune response. However, the regulatory role of m6A in the immune microenvironment in osteoarthritis (OA) remains unclear. Accordingly, we systematically studied RNA modification patterns mediated by 23 m6A regulators in 38 samples and discussed the characteristics of the immune microenvironment modified by m6A. Next, we constructed a novel OA m6A nomogram, an m6A-transcription factor-miRNA network, and a drug network. Healthy and OA samples showed distinct m6A regulatory factor expression patterns. YTHDF3 expression was upregulated in OA samples and positively correlated with type II helper cells and TGFb family member receptors. Furthermore, three different RNA modification patterns were mediated by 23 m6A regulatory factors; in Mode 3, the expression levels of YTHDF3, type II T helper cells, and TGFb family member receptors were upregulated. Pathways related to endoplasmic reticulum oxidative stress and mitochondrial autophagy showed a strong correlation with the regulatory factors associated with Mode 3 and 23 m6A regulatory factors. Through RT-qPCR we validated that SREBF2 and EGR1 as transcription factors of YTHDF3 and IGF2BP3 are closely associated with the development of OA, hsa-miR-340 as a miRNA for YTHDF3 and IGF2BP3 was involved in the development of OA, we also detected the protein expression levels of IGF2BP3, YTHDF3, EGR1 and SREBF2 by western blotting, and the results were consistent with PCR. Overall, the constructed nomogram can facilitate the prediction of OA risk.

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“…The immune-desert and immune-excluded phenotypes can be considered as non-in ammatory tumors, with little or no immune cell in ltration in the TME. The immunein ammatory phenotype was known as a thermo tumor and was characterized by extensive immune cell in ltrates in the TME [32][33][34][35]. Although a large number of immune cells also existed in the immuneexcluded phenotype, they only existed in the stroma around the tumor cell nest and failed to break through the tumor matrix to kill tumor cells or inhibit tumor cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

M5C modulator mediated methylation pattern and TME cell infiltration in bladder cancer

Zhan

Lang

Tao

et al. 2022

Preprint

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Background: In recent studies, the role of modification patterns of N6-methyladenosine (m6A) regulators in tumor microenvironment (TME) cell infiltration in the tumor microenvironment has been identified. However, the role of 5-methylcytosine (m5C) modification patterns in TME cell infiltration remains to be discovered. Methods: In this study, 660 bladder cancer patients were enrolled to comprehensively evaluate the m5C modification pattern based on 13 m5C regulators, and to explore the association between m5C modification pattern and TME cell infiltration status. Finally, PRINCIPAL component analysis (PCA) algorithm constructed m5Cscore, which was used to evaluate and quantify individual m5C modification patterns. Results: Our study identified three distinct m5C modification patterns in bladder cancer. Studies showed that TME cell infiltration characteristics under these three modification patterns were highly associated with three tumor immunophenotypes (immune-inflamed, immune-excluded, immune-desert). In addition, m5C methylation modification patterns were proved to be able to predict tumor disease progression, genetic variation and prognosis of patients. The individualized scoring system – m5Cscore, which was based on m5C methylation modification, showed great differences in tumor mutation burden (TMB), clinical characteristics, immune checkpoint and immunotherapy. The low m5Cscore group was characterized by matrix activation and lack of effective immune cell infiltration, indicating the immune-excluded phenotype. The higher m5Cscore group showed fewer PD-L1 mutations, which were associated with a promoted response to PD-L1/PD-1 immunotherapy and a better prognosis. Conclusions: This work confirmed the extensive regulatory mechanisms of the m5C modification pattern in the tumor microenvironment. The m5C modification pattern functioned as an important element of forming the heterogeneity and complexity of TME landscape. Understanding and in-depth evaluation of individual m5C modification patterns would help us understand the TME landscape and guide better immunotherapy strategies.

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m6A regulator-mediated methylation modification patterns and tumor microenvironment infiltration characterization in hepatocellular carcinoma

Cited by 18 publications

References 34 publications

Application of m6A and TME in Predicting the Prognosis and Treatment of Clear Cell Renal Cell Carcinoma

Application of m6A and TME in Predicting the Prognosis and Treatment of Clear Cell Renal Cell Carcinoma

m6A Regulator-Mediated RNA Methylation Modification Patterns Regulate the Immune Microenvironment in Osteoarthritis

M5C modulator mediated methylation pattern and TME cell infiltration in bladder cancer

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