N7-Methylguanosine Regulatory Genes Profoundly Affect the Prognosis, Progression, and Antitumor Immune Response of Hepatocellular Carcinoma

Zhou, Kailiang; Yang, Jiaqun; Li, Xiaoyan; Wang, Xiong; Zhang, Pengbin; Zhang, Xuqing

doi:10.3389/fsurg.2022.893977

Cited by 7 publications

(4 citation statements)

References 44 publications

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“…Previous studies found m7GRGs expression in ovarian cancer (OC) is significantly correlated with immune cells (involving CD4 + memory resting T cells, plasma cells, and Macrophages M1) (Zheng et al, 2022). In Hepatocellular carcinoma high m7G risk led to a decreased infiltration level of CD8 + T cells, whereas it increased the infiltration levels of Tregs and macrophages (Zhou et al, 2022). METTL1 expression was enhanced in HCC, accompanied by increased CD11b CD15 polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs) and decreased CD8 T cells.…”

Section: Discussionmentioning

confidence: 94%

Identification and verification of m7G-Related genes as biomarkers for prognosis of sarcoma

et al. 2023

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Background: Increasing evidence indicates a crucial role for N7-methylguanosine (m7G) methylation modification in human disease development, particularly cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. However, the role of m7G in sarcomas (SARC) has not been adequately evaluated.Materials and methods: Transcriptome and clinical data were gathered from the TCGA database for this study. Normal and SARC groups were compared for the expression of m7G-related genes (m7GRGs). The expression of m7GRGs was verified using real-time quantitative PCR (RT-qPCR) in SARC cell lines. Then, differentially expressed genes (DEGs) were identified between high and low m7GRGs expression groups in SARC samples, and GO enrichment and KEGG pathways were evaluated. Next, prognostic values of m7GRGs were evaluated by Cox regression analysis. Subsequently, a prognostic model was constructed using m7GRGs with good prognostic values by Lasso regression analysis. Besides, the relationships between prognostic m7GRGs and immune infiltration, clinical features, cuproptosis-related genes, and antitumor drugs were investigated in patients with SARC. Finally, a ceRNA regulatory network based on m7GRGs was constructed.Results: The expression of ten m7GRGs was higher in the SARC group than in the control group. DEGs across groups with high and low m7GRGs expression were enriched for adhesion sites and cGMP-PKG. Besides, we constructed a prognostic model that consists of EIF4A1, EIF4G3, NCBP1, and WDR4 m7GRGs for predicting the survival likelihood of sarcoma patients. And the elevated expression of these four prognostic m7GRGs was substantially associated with poor prognosis and elevated expression in SARC cell lines. Moreover, we discovered that these four m7GRGs expressions were negatively correlated with CD4+ T cell levels, dendritic cell level and tumor purity, and positively correlated with tumor mutational burden, microsatellite instability, drug sensitivity and cuproptosis-related genes in patients with sarcomas. Then, a triple regulatory network of mRNA, miRNA, and lncRNA was established.Conclusion: The current study identified EIF4A1, EIF4G3, NCBP1, and WDR4 as prognostic genes for SARC that are associated with m7G.These findings extend our knowledge of m7G methylation in SARC and may guide the development of innovative treatment options.

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Section: Discussionmentioning

confidence: 94%

Identification and verification of m7G-Related genes as biomarkers for prognosis of sarcoma

et al. 2023

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“…Transcribed mRNAs are bound and escorted to the cytoplasm by the CBC for further translation and modification 15,16 . It is, therefore, understandable that NCBP2 is highly expressed in various tumors, including lung cancer, and is associated with their poor prognosis 45,46 . However, whether NCBP2 has selectivity in term of mRNA translation is still largely unknown.…”

Section: Discussionmentioning

confidence: 99%

“…15,16 It is, therefore, understandable that NCBP2 is highly expressed in various tumors, including lung cancer, and is associated with their poor prognosis. 45,46 However, whether NCBP2 has selectivity in term of mRNA translation is still largely unknown. EIF4E1 functions based on m7G cap structure in cytoplasm.…”

Section: Discussionmentioning

confidence: 99%

m7G‐related genes—NCBP2 and EIF4E3 determine immune contexture in head and neck squamous cell carcinoma by regulating CCL4/CCL5 expression

Zhao

Ying

et al. 2023

Molecular Carcinogenesis

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Aberrant N 7 -methylguanosine (m7G) levels closely correlate with tumor genesis and progression. NCBP2 and EIF4E3 are two important m7G-related cap-binding genes.This study aimed to identify the relationship between the EIF4E3/NCBP2 function and immunological characteristics of head and neck squamous cell carcinoma (HNSCC). Hierarchical clustering was employed in classifying HNSCC patients into two groups based on the expressions of NCBP2 and EIF4E3. The differentially expressed genes were identified between the two groups, and GO functional enrichment was subsequently performed. Weighted gene co-expression network analysis was conducted to identify the hub genes related to EIF4E3/NCBP2 expression and immunity. The differential infiltration of immune cells and the response to immunotherapy were compared between the two groups. Single-cell sequence and trajectory analyses were performed to predict cell differentiation and display the expression of EIF4E3/NCBP2 in each state. In addition, quantitative real-time PCR, spatial transcriptome analysis, transwell assay, and western blotting were conducted to verify the biological function of EIF4E3/NCBP2. Here, group A showed a higher EIF4E3 expression and a lower NCBP2 expression, which had higher immune scores, proportion of most immune cells, immune activities, expression of immunomodulatory targets, and a better response to cancer immunotherapy.Besides, 56 hub molecules with notable immune regulation significance were identified. A risk model containing 17 hub genes and a prognostic nomogram was successfully established. Moreover, HNSCC tissues had a lower EIF4E3 expression and a higher NCBP2 expression than normal tissues. NCBP2 and EIF4E3 played a vital role in the differentiation of monocytes. Furthermore, the expression of CCL4/CCL5 can be regulated via EIF4E3 overexpression and NCBP2 knockdown. Collectively,

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“…Various prognostic models for m7G-related genes in lower-grade gliomas have emerged, however, the models are not well developed (Wang, Zhong et al 2022). Furthermore, m7G-related genes are directly and extensively correlated with tumor microenvironment and immune cells (Wu, Li et al 2022, Zhou, Yang et al 2022.…”

Section: Introductionmentioning

confidence: 99%

Development, validation, and updating of prognostic models for m7G- associated genes in lower-grade gliomas

Li,

Sun,

Geng

et al. 2023

Preprint

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Background Studies are aiming at developing prognostic models using N7-methylguanosine (m7G)-related genes in gliomas, however, models with good predictive performance for lower-grade gliomas have yet to be developed. Methods Based on genes with m7G variants and clinical information, two prediction models have been derived to predict the probability of survival for patients with lower-grade gliomas in TCGA. The models were externally validated using independent datasets. Based on CGGA information, updated models that were created matched the features of the local population. Results Two models were derived, validated and updated. Model 1, which was derived on the basis of mRNA, only contains five genes: CD37, EIF3A, CALU, COLGALT1, and DDX3X. Model 2 included six variables: grade, age, gender, IDH mutation status, 1p/19q codeletion status and prognostic index of model 1. The C-statistic of revised model 1 was 0.764 (95%CI: 0.730–0.798) in the revised set and 0.700 (95%CI: 0.658–0.742) in the test set. Regarding internal validation, C-statistic for model 2 with 1000 bootstrap replications was 0.848, while in external validation, the C-statistic was 0.752 (95%CI: 0.714–0.788). Both models exhibited satisfactory calibration after updating in external validation. The models' web calculator is provided at https://lhj0520.shinyapps.io/M7G-LGG_model/. Conclusion we developed and validated two models and updated them, which makes the models better predictors for patients.

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N7-Methylguanosine Regulatory Genes Profoundly Affect the Prognosis, Progression, and Antitumor Immune Response of Hepatocellular Carcinoma

Cited by 7 publications

References 44 publications

Identification and verification of m7G-Related genes as biomarkers for prognosis of sarcoma

Identification and verification of m7G-Related genes as biomarkers for prognosis of sarcoma

m7G‐related genes—NCBP2 and EIF4E3 determine immune contexture in head and neck squamous cell carcinoma by regulating CCL4/CCL5 expression

Development, validation, and updating of prognostic models for m7G- associated genes in lower-grade gliomas

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