Identification of m6A methyltransferase-related genes predicts prognosis and immune infiltrates in head and neck squamous cell carcinoma

Zhang, Yijian; Li, Li; Ye, Zhihui; Zhang, Lei; Yao, Ninghua; Gai, Ling

doi:10.21037/atm-21-4712

Cited by 16 publications

(13 citation statements)

References 41 publications

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“…These therapies have the potential to reduce the burden of disease associated with HPV infection and improve the quality of life of patients [29]. However, the role and mechanism of m6A in the tumor immune response in HPV-associated cancers are not well defined [26,[30][31][32].…”

Section: Ivyspringmentioning

confidence: 99%

Integrative Analyses of m6A Regulators Identify that METTL3 is Associated with HPV Status and Immunosuppressive Microenvironment in HPV-related Cancers

Yu¹,

Ye²,

He³

et al. 2022

Int. J. Biol. Sci.

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Although m6A modifications are associated with tumor progression, and anti-tumor immune responses, the role of m6A regulators in HPV-related carcinogenesis has not been well resolved. To provide evidence for the role of m6A regulators in HPV-related carcinogenesis and identify potential therapeutic targets for HPV-related cancers, integrative analyses of m6A regulators in 1,485 head and neck squamous cell carcinoma (HNSC) patients and 507 cervical squamous cell carcinoma (CESC) patients was performed and identified that an m6A regulator, METTL3, was highly expressed in tumors and was related to the poor prognosis in HNSC and CESC. In HPV-positive tumors, METTL3 was positively associated with tumor HPV status, such as HPV integration status, E6 and unspliced-E6 expression, and p16 expression. Further analysis demonstrated that METTL3 high status was negatively correlated with tumor immune cell infiltrations and facilitated the expression of immunosuppressive immune checkpoint molecules (i.e., PD-L1). Cell-derived xenograft models demonstrated that METTL3 inhibitor combined with anti-PD1 therapy promoted immunotherapy of CESC in vivo. Overall, this study identified that METTL3 high status, is associated with poor prognosis and HPV status, and serves as a mediator of the immunosuppressive tumor microenvironment in HPV-associated cancer, which provides a promising therapeutic target for anti-cancer immunotherapy.

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Section: Ivyspringmentioning

confidence: 99%

Integrative Analyses of m6A Regulators Identify that METTL3 is Associated with HPV Status and Immunosuppressive Microenvironment in HPV-related Cancers

Yu¹,

Ye²,

He³

et al. 2022

Int. J. Biol. Sci.

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“… Cancer type HnRNPs Expression Role Clinical correlation Detection methods Ref. MNs hnRNPA0 Downregulated Anti-cancer Pathologic differentiation Database [ 23 ] MM hnRNPA2/B1 Upregulated Oncogenic OS qRT-PCR [ 86 ] Glioblastoma hnRNPA2/B1 Upregulated Oncogenic Survival Database, qRT-PCR [ 81 ] OSCC hnRNPA1 Upregulated Oncogenic Clinicopathologic stages IHC, western blot [ 47 ] HNSCC hnRNPA2/B1 Upregulated - OS, DSS Database [ 158 ] LC hnRNPA1 Upregulated Oncogenic OS IHC, western blot, qRT-PCR [ 32 , 33 ] hnRNPA2/B1 Upregulated Oncogenic Lung development, early diagnosis, TNM stage, survival Database, IHC, western blot; northern blot [ 75 , 77 , 93 , 159 ] BC hnRNPA2/B1 Conflicting Conflicting Survival IHC, mRNA-sqe, northern blot [ 101 , 106 , 107 , 160 ] ESCA hnRNPA0 Upregulated Oncogenic …”

Section: Discussionmentioning

confidence: 99%

Heterogeneous nuclear ribonucleoprotein A/B: an emerging group of cancer biomarkers and therapeutic targets

Wang

et al. 2022

Cell Death Discov.

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Heterogeneous nuclear ribonucleoprotein A/B (hnRNPA/B) is one of the core members of the RNA binding protein (RBP) hnRNPs family, including four main subtypes, A0, A1, A2/B1 and A3, which share the similar structure and functions. With the advance in understanding the molecular biology of hnRNPA/B, it has been gradually revealed that hnRNPA/B plays a critical role in almost the entire steps of RNA life cycle and its aberrant expression and mutation have important effects on the occurrence and progression of various cancers. This review focuses on the clinical significance of hnRNPA/B in various cancers and systematically summarizes its biological function and molecular mechanisms.

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“…According to previous studies, HNRNPC has been reported to regulate immunosuppressive events in tumor microenvironment [ 61 , 62 ], and we conducted comparable analyses on HNRNPC to uncover its role in immune systems. Among them, representative methods including ESTIMATE algorithm and ssGSEA were applied to evaluate the immune infiltration level.…”

Section: Discussionmentioning

confidence: 99%

Essential m6A Methylation Regulator HNRNPC Serves as a Targetable Biomarker for Papillary Renal Cell Carcinoma

Wei

Miao

et al. 2022

Journal of Oncology

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m6A RNA modification is a common abundant posttranscriptional modification of mRNAs occurring in cancer growth and progression. Accumulated evidence has proved that HNRNPC, which acts as a m6A reader, plays an essential role in the promotion of cancer occurrence and development; nevertheless, the role of HNRNPC in papillary renal cell carcinoma remained to be discovered. In this study, we comprehensively identified HNRNPC as a hub gene involved in m6A modification in pRCC. Then, the expression level, survival outcomes, PPI network, function enrichment, immune cell infiltration, and single-cell analysis were performed. Finally, we found that HNRNPC significantly promoted renal cell carcinoma proliferation and migration in vitro. In conclusion, our work proved that HNRNPC may act as a momentous m6A regulator, as well as a potential targetable biomarker for pRCC.

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Identification of m6A methyltransferase-related genes predicts prognosis and immune infiltrates in head and neck squamous cell carcinoma

Cited by 16 publications

References 41 publications

Integrative Analyses of m6A Regulators Identify that METTL3 is Associated with HPV Status and Immunosuppressive Microenvironment in HPV-related Cancers

Integrative Analyses of m6A Regulators Identify that METTL3 is Associated with HPV Status and Immunosuppressive Microenvironment in HPV-related Cancers

Heterogeneous nuclear ribonucleoprotein A/B: an emerging group of cancer biomarkers and therapeutic targets

Essential m6A Methylation Regulator HNRNPC Serves as a Targetable Biomarker for Papillary Renal Cell Carcinoma

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