A Prognostic Molecular Signature of N⁶-Methyladenosine Methylation Regulators for Soft-Tissue Sarcoma from The Cancer Genome Atlas Database

Hou, Mingming; Guo, Xiaohui; Chen, Yu; Cong, Lidan; Pan, Changwu

doi:10.12659/msm.928400

Cited by 21 publications

(18 citation statements)

References 24 publications

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“… 31 These findings indicate that the 14-gene signature may play a critical role in the development and progression of sarcomas and may serve as a prognostic tool. In contrast to previous studies, 32 , 33 , 34 the novel IRG signature proved to be suitable for different sarcoma subtypes. The present results suggest that although sarcoma subtypes are partially heterogeneous, these entities share a common genetic background.…”

Section: Discussioncontrasting

confidence: 78%

A novel immune-related gene signature predicting survival in sarcoma patients

Ren

Bazhin

Pretzsch

et al. 2022

Molecular Therapy - Oncolytics

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Sarcomas are a heterogeneous group of rare mesenchymal tumors. The migration of immune cells into these tumors and the prognostic impact of tumor-specific factors determining their interaction with these tumors remain poorly understood. The current risk stratification system is insufficient to provide a precise survival prediction and treatment response. Thus, valid prognostic models are needed to guide treatment. This study analyzed the gene expression and outcome of 980 sarcoma patients from seven public datasets. The abundance of immune cells and the response to immunotherapy was calculated. Immune-related genes (IRGs) were screened through a weighted gene co-expression network analysis (WGCNA). A least absolute shrinkage and selection operator (LASSO) Cox regression was used to establish a powerful IRG signature predicting prognosis. The identified IRG signature incorporated 14 genes and identified highrisk patients in sarcoma cohorts. The 14-IRG signature was identified as an independent risk factor for overall and disease-free survival. Moreover, the IRG signature acted as a potential indicator for immunotherapy. The nomogram based on the risk score was built to provide a more accurate survival prediction. The decision tree with IRG risk score discriminated risk subgroups powerfully. This proposed IRG signature is a robust biomarker to predict outcomes and treatment responses in sarcoma patients.

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Section: Discussioncontrasting

confidence: 78%

A novel immune-related gene signature predicting survival in sarcoma patients

Ren

Bazhin

Pretzsch

et al. 2022

Molecular Therapy - Oncolytics

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“…Tumor angiogenesis can also support chemoresistance and EMT formation as well as apoptosis inhibition. Indeed, some of the lesser reported m 6 A "readers" may also support tumor progression, high expression of YTHDC2 may increase mutation frequency in favor of tumorigenesis and portend a poor prognosis for patients with soft tissue sarcoma [ 265 ].…”

Section: A Methylation Regulates the Biological Functions Of Tumor Cellsmentioning

confidence: 99%

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

et al. 2022

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The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, and immunosuppression. One of the most common RNA modifications, N6-methyladenosine (m6A) methylation, is widely involved in the regulation of physiological and pathological processes, including tumor development. Compelling evidence indicates that m6A methylation regulates transcription and protein expression through shearing, export, translation, and processing, thereby participating in the dynamic evolution of TME. Specifically, m6A methylation-mediated adaptation to hypoxia, metabolic dysregulation, and phenotypic shift of immune cells synergistically promote the formation of an immunosuppressive TME that supports tumor proliferation and metastasis. In this review, we have focused on the involvement of m6A methylation in the dynamic evolution of tumor-adaptive TME and described the detailed mechanisms linking m6A methylation to change in tumor cell biological functions. In view of the collective data, we advocate treating TME as a complete ecosystem in which components crosstalk with each other to synergistically achieve tumor adaptive changes. Finally, we describe the potential utility of m6A methylation-targeted therapies and tumor immunotherapy in clinical applications and the challenges faced, with the aim of advancing m6A methylation research.

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“…Due to diverse histopathological classification, STS has not been fully understood so far, which received widespread attention ( Trojani et al, 1984 ). A previous study constructed an m6A-related risk model to predict the prognosis of STS ( Hou et al, 2020 ). However, different m6A modification patterns were not analyzed comprehensively.…”

Section: Discussionmentioning

confidence: 99%

Molecular Characteristics of m6A Regulators and Tumor Microenvironment Infiltration in Soft Tissue Sarcoma: A Gene-Based Study

Xiao

Yang

Yan

et al. 2022

Front. Bioeng. Biotechnol.

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Background: N6-methyladenosine (m6A) methylation played a key role in tumor growth. However, the relationship between m6A and soft tissue sarcoma (STS) was still unclear.Methods: The characterization and patterns of m6A modification in STS (TCGA-SARC and GSE17674) were analyzed comprehensively through bioinformatics and real-time polymerase chain reaction (RT-PCR). The effects of different m6A modification patterns on prognosis and immune infiltration of STS were further explored. Differentially expressed gene (DEG) analysis was performed. Moreover, an m6Ascore was constructed by principal component analysis (PCA). In addition, two immunotherapy datasets (IMvigor210 and GSE78220) and a sarcoma dataset (GSE17618) were used to evaluate the m6Ascore.Results: Huge differences were found in somatic mutation, CNV, and expression of 25 m6A regulators in STS. Two modification patterns (A and B) in STS were further identified and the m6A cluster A showed a better clinical outcome with a lower immune/stromal score compared with the m6A cluster B (p < 0.050).In addition to , most STS samples from m6A cluster A showed a high m6Ascore, which was related to mismatch repair and a better prognosis of STS (p < 0.001). In contrast, the m6A cluster B, characterized by a low m6Ascore, was related to the MYC signaling pathway, which led to a poor prognosis of STS. A high m6Ascore also contributed to a better outcome of PD-1/PD-L1 blockade immunotherapy.Conclusion: The modification patterns of 25 m6A regulators in the STS microenvironment were explored comprehensively. The novel m6Ascore effectively predicted the characteristics of the tumor microenvironment (TME) and outcome in STS and provided novel insights for future immunotherapy.

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A Prognostic Molecular Signature of N⁶-Methyladenosine Methylation Regulators for Soft-Tissue Sarcoma from The Cancer Genome Atlas Database

Cited by 21 publications

References 24 publications

A novel immune-related gene signature predicting survival in sarcoma patients

A novel immune-related gene signature predicting survival in sarcoma patients

Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

Molecular Characteristics of m6A Regulators and Tumor Microenvironment Infiltration in Soft Tissue Sarcoma: A Gene-Based Study

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