m6A RNA Methylation Regulator YTHDF1 Correlated With Immune Microenvironment Predicts Clinical Outcomes and Therapeutic Efficacy in Breast Cancer

Hu, Ying; Pan, Qinwen; Wang, Minghao; Ai, Xiang; Yan, Yuzhao; Tian, Yuan; Jing, Yuting; Tang, Peng; Jiang, Jun

doi:10.3389/fmed.2021.667543

Cited by 13 publications

(13 citation statements)

References 33 publications

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“…However, the relevance of METTL16 and ZC3H13 in cervical cancer is still not fully known. Recent studies have also focused on immune-related prognostic features associated with cancer immune invasion (36). For example, a growing body of literature strongly suggested that YTHDF1 may regulate the immune microenvironment of breast cancer, influencing tumor growth as well as immunotherapy efficacy (36).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have also focused on immune-related prognostic features associated with cancer immune invasion (36). For example, a growing body of literature strongly suggested that YTHDF1 may regulate the immune microenvironment of breast cancer, influencing tumor growth as well as immunotherapy efficacy (36). According to a recent study, YTHDF1 and YTHDF2 induced inflammation in the TIME in non-small-cell lung cancer (37).…”

Section: Discussionmentioning

confidence: 99%

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Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer

Zhang

Liu

et al. 2022

Front. Immunol.

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Understanding the role of N6-adenosine methylation (m6A) in the tumor microenvironment (TME) is important since it can contribute to tumor development. However, the research investigating the association between m6A and TME and cervical cancer is still in its early stages. The aim of this study was to discover the possible relationship between m6A RNA methylation regulators, TME, PD-L1 expression levels, and immune infiltration in cervical cancer. We gathered RNA-seq transcriptome data and clinical information from cervical cancer patients using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases. To begin, researchers assessed the differences in m6A regulatory factor expression levels between cervical cancer and normal tissues. Clustering analysis was adapted to assess PD-L1 expression, immunological score, immune cell infiltration, TME, and probable pathways in cervical cancer samples. The majority of m6A regulators were found to be considerably overexpressed in cervical cancer tissues. Using consensus clustering of 21 m6A regulators, we identified two subtypes (clusters 1/2) of cervical cancer, and we found that WHO stage and grade were associated with the subtypes. PD-L1 expression increased dramatically in cervical cancer tissues and was significantly linked to ALKBH5, FTO, METTL3, RBM15B, YTHDF1, YTHDF3, and ZC3H13 expression levels. Plasma cells and regulatory T cells (Tregs) were considerably elevated in cluster 2. Cluster 1 is involved in numerous signature pathways, including basal transcription factors, cell cycle, RNA degradation, and the spliceosome. The prognostic signature-based riskscore (METTL16, YTHDF1, and ZC3H13) was found to be an independent prognostic indicator of cervical cancer. The tumor immune microenvironment (TIME) was linked to m6A methylation regulators, and changes in their copy number will affect the quantity of tumor-infiltrating immune cells dynamically. Overall, our research discovered a powerful predictive signature based on m6A RNA methylation regulators. This signature correctly predicted the prognosis of cervical cancer patients. The m6A methylation regulator could be a critical mediator of PD-L1 expression and immune cell infiltration, and it could have a significant impact on the TIME of cervical cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer

Zhang

Liu

et al. 2022

Front. Immunol.

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“…The changes of TIME play a signi cant role in the progression of LUAD (51,52). YTHDF1, as a m6A modi cation regulator gene, plays a signi cant role in immune regulation of various cancers (53)(54)(55). In this study, the group with low expression of YTHDF1 had higher in ltration levels of activated B cell, activated dendritic cell, eosinophil, immature B cell, T follicular helper cell, immature dendritic cell, macrophage, mast cell, type 1 T helper cell, monocyte, plasmacytoid dendritic cell and type 17 T helper cell.…”

Section: Discussionmentioning

confidence: 99%

Uncovering the relationship between YTHDF1 related to immune cells and prognosis and diagnosis in lung adenocarcinoma

Han

Liu

et al. 2022

Preprint

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Background As a regulator of m6A modification, YTHDF1 is involved in regulating the pathological mechanism of cancer. However, the molecular characteristics and roles of YTHDF1 in (LUAD) remain to be further elucidated. The purpose of this study was to identify potential molecular characteristics of YTHDF1 through bioinformatics analysis, hoping to lay a theoretical foundation for LUAD management. Methods All information was downloaded from public databases. Then, the expression of YTHDF1 in LUAD was analyzed. The competing endogenous RNA (ceRNA) network was built to explore the molecular interactions. Subsequently, LUAD were divided into two groups on account of the median YTHDF1 expression. The differences in survival and immune cell infiltration between the two groups were analyzed. Genes associated with YTHDF1 were identified based on the WGCNA. Results YTHDF1 was up-regulated in tumor tissues and may be a new diagnostic biomarker of LUAD. In ceRNA network, YTHDF1, 7 miRNAs and 17 lncRNAs were included. Increased YTHDF1 expression was significantly connected with poor prognosis of LUAD. The expression level of YTHDF1 was also negatively correlated with the infiltration of most immune cells. Moreover, an increase in YTHDF1 copy number can lead to a decrease in the level of CD4 + T cell infiltration. The calibration curves indicated that nomogram constructed by YTHDF1 and clinical parameters showed higher accuracy in overall survival prediction at 1 and 2 years. Conclusion High expression of YTHDF1 was associated with poor prognosis and immune dysregulation in LUAD. The study of the molecular characteristics of YTHDF1 in LUAD can be helpful for disease management.

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“…Melanoma patients treated with anti-PD-1 therapy benefited from ALKBH5 deletion [ 106 ]. Furthermore, the latest research found that a large number of immune checkpoint receptors (including PD-1, TIM-3, and CTLA-4) as well as lymphocytes infiltrating (such as B cells, T cells, macrophages, and dendritic cells) positively correlated with the level of m 6 A readers YTHDF1, and YTHDF2 in respective cancer type, including glioma, NSCLC, kidney renal clean cell carcinoma and BC [ 107 – 110 ]. Despite the different TIME among tumor types and individual responses, correcting m 6 A regulator disorder was a feasible strategy for cancer immunotherapy (Fig.…”

Section: Mechanisms Of M 6 A-mediated Drug Resistancementioning

confidence: 99%

Biological and pharmacological roles of m6A modifications in cancer drug resistance

et al. 2022

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Cancer drug resistance represents the main obstacle in cancer treatment. Drug-resistant cancers exhibit complex molecular mechanisms to hit back therapy under pharmacological pressure. As a reversible epigenetic modification, N6-methyladenosine (m6A) RNA modification was regarded to be the most common epigenetic RNA modification. RNA methyltransferases (writers), demethylases (erasers), and m6A-binding proteins (readers) are frequently disordered in several tumors, thus regulating the expression of oncoproteins, enhancing tumorigenesis, cancer proliferation, development, and metastasis. The review elucidated the underlying role of m6A in therapy resistance. Alteration of the m6A modification affected drug efficacy by restructuring multidrug efflux transporters, drug-metabolizing enzymes, and anticancer drug targets. Furthermore, the variation resulted in resistance by regulating DNA damage repair, downstream adaptive response (apoptosis, autophagy, and oncogenic bypass signaling), cell stemness, tumor immune microenvironment, and exosomal non-coding RNA. It is highlighted that several small molecules targeting m6A regulators have shown significant potential for overcoming drug resistance in different cancer categories. Further inhibitors and activators of RNA m6A-modified proteins are expected to provide novel anticancer drugs, delivering the therapeutic potential for addressing the challenge of resistance in clinical resistance.

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m6A RNA Methylation Regulator YTHDF1 Correlated With Immune Microenvironment Predicts Clinical Outcomes and Therapeutic Efficacy in Breast Cancer

Cited by 13 publications

References 33 publications

Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer

Comprehensive characterization of tumor microenvironment and m6A RNA methylation regulators and its effects on PD-L1 and immune infiltrates in cervical cancer

Uncovering the relationship between YTHDF1 related to immune cells and prognosis and diagnosis in lung adenocarcinoma

Biological and pharmacological roles of m6A modifications in cancer drug resistance

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