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EIF3M as a pan-cancer biomarker: prognostic significance and immune infiltration association
Front Mol Biosci. 2025 Nov 18;12:1697083. doi: 10.3389/fmolb.2025.1697083. eCollection 2025.
ABSTRACT
BACKGROUND: EIF3M, a core subunit of eukaryotic translation initiation factor 3, plays a pivotal role in protein synthesis by regulating the assembly of the 43S initiation complex. However, its biological functions in cancer remain poorly understood. To further investigate the clinical translational value and underlying mechanisms of EIF3M in tumors, this study conducted comprehensive bioinformatic analysis of EIF3M across various tumor types.
METHODS: We utilized publicly available databases to perform a comprehensive bioinformatics analysis of EIF3M's biological roles in oncogenesis, aiming to elucidate its pan-cancer expression patterns and prognostic significance. Furthermore, we conducted an integrative multi-omics analysis incorporating methylation profiling, co-expressed gene networks, targeted miRNA interactions, and tumor immune microenvironment infiltration to decipher the complex regulatory architecture and biological pathways mediated by EIF3M across cancer types. Finally, we used HCC cell lines for in vitro functional validation, determining how EIF3M expression modulates malignant phenotypic behaviors in hepatocellular carcinoma.
RESULTS: EIF3M was overexpressed in multiple cancers and correlated with advanced tumor stage and poor survival. Its dysregulation was primarily driven by gene amplification and regulated by promoter methylation and miRNAs. EIF3M functioned as a hub in cell cycle and transcriptional networks and was linked to an immunosuppressive microenvironment. In hepatocellular carcinoma models, EIF3M modulated tumor proliferation, migration, and activated oncogenic pathways like Wnt/β-catenin.
CONCLUSION: This study reveals that EIF3M expression correlates with immune infiltration and poor prognosis in multiple cancers. In vitro experiments in hepatocellular carcinoma models demonstrated that EIF3M critically regulates malignant cell behaviors. Collectively, our findings highlight EIF3M's value as a promising pan-cancer biomarker worthy of further investigation for its utility in prognosis prediction and as an indicator of immunotherapeutic response.
PMID:41341921 | PMC:PMC12669982 | DOI:10.3389/fmolb.2025.1697083
EIF3M as a pan-cancer biomarker: prognostic significance and immune infiltration association
Front Mol Biosci. 2025 Nov 18;12:1697083. doi: 10.3389/fmolb.2025.1697083. eCollection 2025.
ABSTRACT
BACKGROUND: EIF3M, a core subunit of eukaryotic translation initiation factor 3, plays a pivotal role in protein synthesis by regulating the assembly of the 43S initiation complex. However, its biological functions in cancer remain poorly understood. To further investigate the clinical translational value and underlying mechanisms of EIF3M in tumors, this study conducted comprehensive bioinformatic analysis of EIF3M across various tumor types.
METHODS: We utilized publicly available databases to perform a comprehensive bioinformatics analysis of EIF3M's biological roles in oncogenesis, aiming to elucidate its pan-cancer expression patterns and prognostic significance. Furthermore, we conducted an integrative multi-omics analysis incorporating methylation profiling, co-expressed gene networks, targeted miRNA interactions, and tumor immune microenvironment infiltration to decipher the complex regulatory architecture and biological pathways mediated by EIF3M across cancer types. Finally, we used HCC cell lines for in vitro functional validation, determining how EIF3M expression modulates malignant phenotypic behaviors in hepatocellular carcinoma.
RESULTS: EIF3M was overexpressed in multiple cancers and correlated with advanced tumor stage and poor survival. Its dysregulation was primarily driven by gene amplification and regulated by promoter methylation and miRNAs. EIF3M functioned as a hub in cell cycle and transcriptional networks and was linked to an immunosuppressive microenvironment. In hepatocellular carcinoma models, EIF3M modulated tumor proliferation, migration, and activated oncogenic pathways like Wnt/β-catenin.
CONCLUSION: This study reveals that EIF3M expression correlates with immune infiltration and poor prognosis in multiple cancers. In vitro experiments in hepatocellular carcinoma models demonstrated that EIF3M critically regulates malignant cell behaviors. Collectively, our findings highlight EIF3M's value as a promising pan-cancer biomarker worthy of further investigation for its utility in prognosis prediction and as an indicator of immunotherapeutic response.
PMID:41341921 | PMC:PMC12669982 | DOI:10.3389/fmolb.2025.1697083
LGM: Enhancing Large Language Models with Conceptual Meta-Relations and Iterative Retrieval
Unraveling the role of GPCR signaling in metabolic reprogramming and immune microenvironment of lung adenocarcinoma: a multi-omics study with experimental validation
Front Immunol. 2025 Jun 6;16:1606125. doi: 10.3389/fimmu.2025.1606125. eCollection 2025.
ABSTRACT
BACKGROUND: Lung adenocarcinoma (LUAD) is characterized by metabolic and immune heterogeneity, driving tumor progression and therapy resistance. While G protein-coupled receptors (GPCR) signaling is known to regulate metabolism and immunity in cancers, its role in LUAD remains poorly defined. This study explores the influence of GPCR signaling on LUAD metabolism and immune landscape.
METHODS: We performed non-negative matrix factorization (NMF) clustering of GPCR signaling genes in TCGA-LUAD cohort to identify distinct molecular subgroups. A prognostic model was developed based on GPCR signaling genes using least absolute shrinkage and selection operator (LASSO) analysis and Cox regression. Differentially expressed genes were analyzed for metabolic pathway enrichment and immune infiltration. In addition, key genes within GPCR signaling were identified and validated through functional assays.
RESULTS: NMF clustering based on GPCR signaling identified three subgroups in LUAD, with cluster 3 exhibiting poorer overall survival and significant enrichment in multiple prognostic associated metabolism pathways including purine, pyrimidine, glyoxylate and dicarboxylate metabolism. Then, we developed a GPCRscore prognostic model and validated across multiple cohorts, which effectively stratified LUAD patients into distinct risk groups. High-risk LUAD patients had an immunosuppressive microenvironment and activated metabolic reprogramming. ADM was identified as a key gene in the high-risk group, correlating with tumor stage, immune suppression, and resistance to immunotherapy. Clinically, ADM was highly expressed in tumor tissues and shows elevated concentrations in the peripheral blood of patients with advanced-stage LUAD. Subsequently, we demonstrated that knock-down of ADM in LUAD cells impaired their proliferation, migration, and invasion, while also reducing the angiogenic potential of endothelial cells in vitro. Adrenomedullin promoted LUAD progression in a murine metastasis model. Further, adrenomedullin inhibited CD8+ T cells proliferation, induced exhaustion, and impaired cytotoxic function. Finally, drug sensitivity and cell viability analysis showed LUAD patients with high levels of ADM exhibited sensitivity to the treatment of Staurosporine and Dasatinib.
CONCLUSIONS: In summary, this study reveals the pivotal role of GPCR signaling particularly mediated by ADM in orchestrating metabolic reprogramming and immune modulation in LUAD. ADM emerges as a potential predictive biomarker and therapeutic target, offering valuable implications for optimizing strategies.
PMID:40547013 | PMC:PMC12179119 | DOI:10.3389/fimmu.2025.1606125