m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Cell-Infiltration Characterization in Head and Neck Cancer

Qin, Yang; Xu, Feng; Jian, Aiwen; Yu, Hongmei; Ye, Tao; Hu, Weiqi

doi:10.3389/fcell.2021.803141

Cited by 6 publications

(6 citation statements)

References 41 publications

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“…While prior studies have described distinct epigenetic profiles of cancer-associated fibroblasts and other stromal cell types within the TME ( 29 – 31 ), the impact of direct stromal cell contact on cancer cell chromatin profiles remains unexplored. Therefore, we aimed to investigate the influence of stromal cell contact on tumor cell chromatin accessibility using assay for transposase-accessible chromatin with sequencing (ATAC-seq).…”

Section: Resultsmentioning

confidence: 99%

Cancer–stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies

Goyette,

Stevens,

DePinho

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Brain metastatic breast cancer is particularly lethal largely due to therapeutic resistance. Almost half of the patients with metastatic HER2-positive breast cancer develop brain metastases, representing a major clinical challenge. We previously described that cancer-associated fibroblasts are an important source of resistance in primary tumors. Here, we report that breast cancer brain metastasis stromal cell interactions in 3D cocultures induce therapeutic resistance to HER2-targeting agents, particularly to the small molecule inhibitor of HER2/EGFR neratinib. We investigated the underlying mechanisms using a synthetic Notch reporter system enabling the sorting of cancer cells that directly interact with stromal cells. We identified mucins and bulky glycoprotein synthesis as top-up-regulated genes and pathways by comparing the gene expression and chromatin profiles of stroma-contact and no-contact cancer cells before and after neratinib treatment. Glycoprotein gene signatures were also enriched in human brain metastases compared to primary tumors. We confirmed increased glycocalyx surrounding cocultures by immunofluorescence and showed that mucinase treatment increased sensitivity to neratinib by enabling a more efficient inhibition of EGFR/HER2 signaling in cancer cells. Overexpression of truncated MUC1 lacking the intracellular domain as a model of increased glycocalyx-induced resistance to neratinib both in cell culture and in experimental brain metastases in immunodeficient mice. Our results highlight the importance of glycoproteins as a resistance mechanism to HER2-targeting therapies in breast cancer brain metastases.

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Section: Resultsmentioning

confidence: 99%

Cancer–stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies

Goyette,

Stevens,

DePinho

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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“…The m6A score was used to assess the genetic characteristics of the m6A pattern of ONFH. The m6A pattern was first determined using principal component analysis (PCA), and then the m6A score was calculated by the following formula: m6A score = 6 (PC1i + PC2i) [26][27][28].…”

Section: The Sample's M6a Scorementioning

confidence: 99%

m6A methylation modification and immune infiltration analysis in osteonecrosis of the femoral head

Fang,

Peng,

Lin

et al. 2024

J Orthop Surg Res

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Osteonecrosis of the femoral head (ONFH) is a elaborate hip disease characterized by collapse of femoral head and osteoarthritis. RNA N6-methyladenosine (m6A) plays a crucial role in a lot of biological processes within eukaryotic cells. However, the role of m6A in the regulation of ONFH remains unclear. In this study, we identified the m6A regulators in ONFH and performed subtype classification. We identified 7 significantly differentially expressed m6A regulators through the analysis of differences between ONFH and normal samples in the Gene Expression Omnibus (GEO) database. A random forest algorithm was employed to monitor these regulators to assess the risk of developing ONFH. We constructed a nomogram based on these 7 regulators. The decision curve analysis suggested that patients can benefit from the nomogram model. We classified the ONFH samples into two m6A models according to these 7 regulators through consensus clustering algorithm. After that, we evaluated those two m6A patterns using principal component analysis. We assessed the scores of those two m6A patterns and their relationship with immune infiltration. We observed a higher m6A score of type A than that of type B. Finally, we performed a cross-validation of crucial m6A regulatory factors in ONFH using external datasets and femoral head bone samples. In conclusion, we believed that the m6A pattern could provide a novel diagnostic strategy and offer new insights for molecularly targeted therapy of ONFH.

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“…We used Spearman and distance correlation analyses to calculate the correlation coefficients. 47 Differences between the two groups were assessed using Wilcoxon test and one-way analysis of variance (ANOVA). Further comparison between the groups was conducted using the Kruskal-Wallis test.…”

Section: Correlation Between M6a Score and Somatic Alteration Datamentioning

confidence: 99%

Link between m6A modification and infiltration characterization of tumor microenvironment in lung adenocarcinoma

Yang,

Li,

Zhang

et al. 2023

Exp Biol Med (Maywood)

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N6-methyladenosine (m6A) RNA methylation plays a pivotal role in immune responses and the onset and advancement of cancer. Nonetheless, the precise impact of m6A modification in lung adenocarcinoma (LUAD) and its associated tumor microenvironment (TME) remains to be fully elucidated. Here, we distinguished distinct m6A modification patterns within two separate LUAD cohorts using a set of 21 m6A regulators. The TME characteristics associated with these two patterns align with the immune-inflamed and immune-excluded phenotypes, respectively. We identified 2064 m6A-related genes, which were used as a basis to divide all LUAD samples into three distinct m6A gene clusters. We applied a scoring system to evaluate the m6A gene signature of the m6A modification pattern in individual patients. To authenticate the categorization significance of m6A modification patterns, we established a correlation between m6A score and TME infiltration profiling, tumor somatic mutations, and responses to immunotherapy. A high level of m6A modification may be associated with the aggressiveness and poor prognosis of LUAD. Further studies should investigate the mechanism of action of m6A regulators and m6A-related genes to improve the diagnosis and treatment of patients with LUAD.

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m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Cell-Infiltration Characterization in Head and Neck Cancer

Cited by 6 publications

References 41 publications

Cancer–stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies

Cancer–stromal cell interactions in breast cancer brain metastases induce glycocalyx-mediated resistance to HER2-targeting therapies

m6A methylation modification and immune infiltration analysis in osteonecrosis of the femoral head

Link between m6A modification and infiltration characterization of tumor microenvironment in lung adenocarcinoma

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