Expression profiles of m6A RNA methylation regulators, PD-L1 and immune infiltrates in gastric cancer

Chen, Qiuli; Shu, Lilu; Zhang, Chunye; Liu, Wenjun

doi:10.3389/fonc.2022.970367

Cited by 13 publications

(11 citation statements)

References 61 publications

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“…Immune evasion: METTL3-mediated RNA modification may also play a role in immune evasion by regulating exons. 33 The present meta-analysis involved seven studies and revealed that a high expression level of METTL3 is associated with a poor OS in GC patients. This study has demonstrated that high METTL3 expression was associated with significantly poorer OS (HR = 2.37, 95% CI 1.66-3.39, P < 0.01) and unfavorable DFS (HR = 2.58, 95% CI 1.97-3.38, P < 0.01), as did unfavorable PFS (HR = 1.48, 95% CI 1.19-1.84, P < 0.01)/RFS (HR = 2.62, 95% CI 1.93-5.62, P < 0.01)/PPS (HR = 1.53, 95% CI 1.22-1.91, P < 0.01).…”

Section: Discussionmentioning

confidence: 92%

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Prognostic significance of N6-methyladenosine-modified related chemotransferase METTL3 in gastric carcinoma: Evidence from meta-analysis

Zhu

et al. 2023

Int J Biol Markers

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Background N6-methyladenosine (m6A) methylation is known as the research hotspot for tumor epimodification, and its associated methyltransferase-like3 (METTL3) is significantly differentially expressed in gastric carcinoma, but its clinical value has not been summarized. This meta-analysis aimed to evaluate the prognostic significance of METTL3 in gastric carcinoma. Material and methods Databases, including PubMed, EMBASE (Ovid platform), Science Direct, Scopus, MEDLINE, Google Scholar, Web of Science, and Cochrane Library, were used to identify relevant eligible studies. The endpoints included overall survival, progression-free survival, recurrence-free survival, post-progression survival, and disease-free survival. Hazard ratios (HR) with 95% confidence intervals (CI) were used to correlate METTL3 expression with prognosis. Subgroup and sensitivity analyses were performed. Results Seven eligible studies involving 3034 gastric carcinoma patients were recruited for this meta-analysis. The analysis showed that high METTL3 expression was associated with significantly poorer overall survival (HR = 2.37, 95% CI 1.66–3.39, P < 0.01) and unfavorable disease-free survival (HR = 2.58, 95% CI 1.97–3.38, P < 0.01), as did unfavorable progression-free survival (HR = 1.48, 95% CI 1.19–1.84, P < 0.01)/recurrence-free survival (HR = 2.62, 95% CI 1.93–5.62, P < 0.01)/post-progression survival (HR = 1.53, 95% CI 1.22–1.91, P < 0.01). Subgroup analysis found that high METTL3 expression was associated with worse overall survival in patients with Chinese (HR = 2.21, 95% CI 1.48–3.29, P < 0.01), in studies with sample source from formalin-fixed, paraffin-embedded tissues (HR = 2.66, 95% CI 1.79–3.94, P < 0.01), and the reported directly from articles group (HR = 2.42, 95% CI 1.66–3.53, P < 0.01). The subgroup analysis that was performed based on sample size, detected method, and follow-up showed the same results. Conclusions High expression of METTL3 predicts poor prognosis in gastric carcinoma, indicating promise for METTL3 as a prognostic biomarker. Systematic review registration: https://www.crd.york.ac.uk/prospero , ID = CRD42023408519

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Section: Discussionmentioning

confidence: 92%

“…Immune evasion: METTL3-mediated RNA modification may also play a role in immune evasion by regulating exons. 33…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of N6-methyladenosine-modified related chemotransferase METTL3 in gastric carcinoma: Evidence from meta-analysis

Zhu

et al. 2023

Int J Biol Markers

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“…We identified HNRNPC as a hub gene that interacts with m6A methylation via immune processes and can effectively classify IMSs. Some studies found an association between HNRNPC and tumor progression, 46 , 47 , 48 as well as immune cell infiltration. 49 However, which immune cells can be regulated by HNRNPC , thus remodeling the TME is still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies found an association between HNRNPC and tumor progression, [46][47][48] as well as immune cell infiltration. 49 However, which immune cells can be regulated by HNRNPC, thus remodeling the TME is still unclear.…”

Section: Discussionmentioning

confidence: 99%

HNRNPC suppresses tumor immune microenvironment by activating Treg cells promoting the progression of prostate cancer

Cheng

Wei

et al. 2023

Cancer Science

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Immune microenvironment could affect the biological progress in prostate cancer (PCa) through N6 methyl adenosine (m6A) methylation. The purpose of this study was to investigate the crosstalk between m6A methylation and immune microenvironment and explore potential biomarkers to improve the immunotherapeutic response. Firstly, according to 11 differentially expressed m6A genes between normal and tumor samples, PCa patients were divided into immune microenvironment subtype 1 (IMS1) and IMS2 based on m6A gene profiles extracted from The Cancer Genome Atlas (TCGA) database. IMS2 showed an immune “cold” phenotype with worse prognoses, and HNRNPC was identified as the biomarker of IMS2 by the protein‐protein interaction network. Furthermore, through bioinformatics analyses and in vitro experiments, we found that HNRNPC ‐high patients showed a suppressive immune‐infiltrating tumor microenvironment with a higher infiltration of regulatory T (Treg) cells. Finally, we cocultured transfected PCa cells with peripheral blood mononuclear cells (PBMC) and verified that HNRNPC inhibits tumor immunity by elevating the activation of Treg cells and suppression of effector CD8 T cell. In conclusion, we identified a “cold” immune phenotype in PCa, and HNRNPC regulating the activation of Treg cells. Activation of the immune microenvironment through targeting HNRNPC may be a potential therapeutic option for advanced PCa.

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“…There are 172 identified forms of RNA alterations, and the most common chemical modifications are m6A, m1A, and m5C. m6A is one of the most prevalent eukaryotic mRNA modifications ( 8 ). The m6A modification involves the methylation of adenosine’s sixth nitrogen atom, with Sadenosylmethionine, a cellular methyltransferase substrate, functioning as the methyl donor ( 9 ).…”

Section: Introductionmentioning

confidence: 99%

Constructing and validating of m6a-related genes prognostic signature for stomach adenocarcinoma and immune infiltration: Potential biomarkers for predicting the overall survival

Yang

et al. 2022

Front. Oncol.

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BackgroundStomach adenocarcinoma (STAD) arises from the mutations of stomach cells and has poor overall survival. Chemotherapy is commonly indicated for patients with stomach cancer following surgical resection. The most prevalent alteration that affects cancer growth is N6-methyladenosine methylation (m6A), although the possible function of m6A in STAD prognosis is not recognized.MethodThe research measured predictive FRGs in BLCA samples from the TCGA and GEO datasets. Data on the stemness indices (mRNAsi), gene mutations, copy number variations (CNV), tumor mutation burden (TMB), and corresponding clinical characteristics were obtained from TCGA and GEO. STAD from TCGA and GEO at 24 m6A was investigated. Lasso regression was used to construct the prediction model to assess the m6A prognostic signals in STAD. In addition, the correlation between m6a and immune infiltration in STAD patients was discussed using GSVA and ssGSEA analysis. Based on these genes, GO and KEGG analyses were performed to identify key biological functions and key pathways.ResultA significant relationship was discovered between numerous m6A clusters and the tumor immune microenvironment, as well as three m6A alteration patterns with different clinical outcomes. Furthermore, GSVA and ssGSEA showed that m6A clusters were significantly associated with immune infiltration in the STAD. The low-m6Ascore group had a lower immunotherapeutic response than the high-m6Ascore group. ICIs therapy was more effective in the group with a higher m6Ascore. Three writers (VIRMA, ZC3H13, and METTL3) showed significantly lower expression, whereas five authors (METTL14, METTL16, WTAP, RBM15, and RBM15B) showed considerably higher expression. Three readers (YTHDC2, YTHDF2, and LRPPRC) had higher levels of expression, whereas eleven readers (YTHDC1, YTHDF1, YTHDF3, HNRNPC, FMR1, HNRNPA2B1, IGFBP1, IGFBP2, IGFBP3, and RBMX) had lower levels. As can be observed, the various types of m6 encoders have varied ramifications for STAD control.ConclusionSTAD occurrence and progression are linked to m6A-genes. Corresponding prognostic models help forecast the prognosis of STAD patients. m6A-genes and associated immune cell infiltration in the tumor microenvironment (TME) may serve as potential therapeutic targets in STAD, which requires further trials. In addition, the m6a-related gene signature offers a viable alternative to predict bladder cancer, and these m6A-genes show a prospective research area for STAD targeted treatment in the future.

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Expression profiles of m6A RNA methylation regulators, PD-L1 and immune infiltrates in gastric cancer

Cited by 13 publications

References 61 publications

Prognostic significance of N6-methyladenosine-modified related chemotransferase METTL3 in gastric carcinoma: Evidence from meta-analysis

Prognostic significance of N6-methyladenosine-modified related chemotransferase METTL3 in gastric carcinoma: Evidence from meta-analysis

HNRNPC suppresses tumor immune microenvironment by activating Treg cells promoting the progression of prostate cancer

Constructing and validating of m6a-related genes prognostic signature for stomach adenocarcinoma and immune infiltration: Potential biomarkers for predicting the overall survival

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