{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T14:14:43Z","timestamp":1784297683157,"version":"3.55.0"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer, characterized by a poor prognosis. Many HCC patients are diagnosed at an advanced stage due to the lack of reliable prognostic biomarkers. G6PC1 (Glucose\u20106\u2010Phosphatase Catalytic Subunit 1) is abnormally expressed in various cancers, including HCC. This study aimed to investigate the biomarker potential and biological functions of G6PC1 to elucidate its impact on HCC pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>G6PC1 expression levels were assessed using TCGA and GEO datasets. Prognostic implications were explored through Kaplan-Meier survival analysis. Potential regulatory transcription factors (TFs) were identified using four prediction tools, and functional mechanisms were investigated via GO and KEGG enrichment analyses. Associations between G6PC1 and HCC metabolic reprogramming, as well as the tumor microenvironment were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>G6PC1 exhibited low expression levels in HCC, which correlated with poor patient prognosis. HNF4A may act as a regulatory factor for G6PC1 in HCC. Functional analysis identified co-expressed genes associated with metabolism-related pathways. Furthermore, G6PC1 was implicated in metabolic reprogramming, immune infiltration, and immunotherapy response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Low G6PC1 expression, associated with poor HCC prognosis, is a potential prognostic biomarker. Integrated multi-omics analyses underscore its clinical significance, involvement in metabolic reprogramming, and immunomodulatory functions, providing a foundation for further investigation into its prognostic potential and mechanistic contributions in HCC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1623315","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T05:33:13Z","timestamp":1754026393000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["G6PC1 expression as a prognostic biomarker associated with metabolic reprogramming and tumor microenvironment in hepatocellular carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Xilong","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjin","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2022.2154658","article-title":"Clinical value of identifying genes that inhibit hepatocellular carcinomas","volume":"22","author":"Testa","year":"2022","journal-title":"Expert Rev Mol Diagn"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/s0168-8278(02)00360-4","article-title":"Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy","volume":"38","author":"Imamura","year":"2003","journal-title":"J Hepatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J Clin"},{"key":"B5","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1159\/000509424","article-title":"Guidelines for the diagnosis and treatment of hepatocellular carcinoma (2019 edition)","volume":"9","author":"Zhou","year":"2020","journal-title":"Liver Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/metabo9120282","article-title":"Glucose-6 phosphate, A central hub for liver carbohydrate metabolism","volume":"9","author":"Rajas","year":"2019","journal-title":"Metabolites"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-021-00852-9","article-title":"The trans-ancestral genomic architecture of glycemic traits","volume":"53","author":"Chen","year":"2021","journal-title":"Nat Genet"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.70090","article-title":"The Genetic Polymorphisms of rs161620 and rs2229611 in G6PC 3\u2019UTR Are Associated With Metformin Efficacy in Chinese Type 2 Diabetes Mellitus","volume":"13","author":"Li","year":"2025","journal-title":"Pharmacol Res Perspect"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2024.09.005","article-title":"The role of glucose-6-phosphatase activity in glucose homeostasis and its potential for diabetes therapy","volume":"31","author":"Tan","year":"2025","journal-title":"Trends Mol Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1007\/s13277-015-3463-6","article-title":"Genetic and molecular analyses reveal G6PC as a key element connecting glucose metabolism and cell cycle control in ovarian cancer","volume":"36","author":"Guo","year":"2015","journal-title":"Tumor Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s13046-023-02718-w","article-title":"MiR-494 induces metabolic changes through G6pc targeting and modulates sorafenib response in hepatocellular carcinoma","volume":"42","author":"Bergamini","year":"2023","journal-title":"J Exp Clin Cancer Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.15536","article-title":"Large-scale transcriptome profiles reveal robust 20-signatures metabolic prediction models and novel role of G6PC in clear cell renal cell carcinoma","volume":"24","author":"Xu","year":"2020","journal-title":"J Cell Mol Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"5559","DOI":"10.1016\/j.cell.2021.10.001","article-title":"Glycogen accumulation and phase separation drives liver tumor initiation","volume":"184","author":"Liu","year":"2021","journal-title":"Cell"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2017.01.003","article-title":"Glycogen storage disease type Ia mice with less than 2% of normal hepatic glucose-6-phosphatase-\u03b1 activity restored are at risk of developing hepatic tumors","volume":"120","author":"Kim","year":"2017","journal-title":"Mol Genet Metab"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa407","article-title":"TIMER2.0 for analysis of tumor-infiltrating immune cells","volume":"48","author":"Li","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B16","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neo.2022.01.001","article-title":"UALCAN: An update to the integrated cancer data analysis platform","volume":"25","author":"Chandrashekar","year":"2022","journal-title":"Neoplasia"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/path.2440","article-title":"The Human Protein Atlas\u2013a tool for pathology","volume":"216","author":"Pont\u00e9n","year":"2008","journal-title":"J Pathol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"378","DOI":"10.21147\/j.issn.1000-9604.2024.04.03","article-title":"SOX11 as a potential prognostic biomarker in hepatocellular carcinoma linked to immune infiltration and ferroptosis","volume":"36","author":"Chen","year":"2024","journal-title":"Chin J Cancer Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2196\/27633","article-title":"Web-based survival analysis tool tailored for medical research (KMplot): development and implementation","volume":"23","author":"L\u00e1nczky","year":"2021","journal-title":"J Med Internet Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.2147\/JHC.S483664","article-title":"A gluconeogenesis-related genes model for predicting prognosis, tumor microenvironment infiltration, and drug sensitivity in hepatocellular carcinoma","volume":"11","author":"Tang","year":"2024","journal-title":"J Hepatocell Carcinoma"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac959","article-title":"TISCH2: expanded datasets and new tools for single-cell transcriptome analyses of the tumor microenvironment","volume":"51","author":"Han","year":"2023","journal-title":"Nucleic Acids Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/gpbjnl\/qzae011","article-title":"HCCDB v2.0: decompose expression variations by single-cell RNA-seq and spatial transcriptomics in HCC","volume":"22","author":"Jiang","year":"2024","journal-title":"Genomics Proteomics Bioinf"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000002864","article-title":"Correlation coefficients: appropriate use and interpretation","volume":"126","author":"Schober","year":"2018","journal-title":"Anesth Analg"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2025.2456113","article-title":"Immune infiltration landscape and potential drug-targeted implications for hepatocellular carcinoma with \u201cprogression\/hyper-progression\u201d recurrence","volume":"57","author":"Xu","year":"2025","journal-title":"Ann Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"pl1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci Signal"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.2217\/epi-2017-0118","article-title":"MethSurv: a web tool to perform multivariable survival analysis using DNA methylation data","volume":"10","author":"Modhukur","year":"2018","journal-title":"Epigenomics"},{"key":"B28","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13072-019-0316-3","article-title":"The SMART App: an interactive web application for comprehensive DNA methylation analysis and visualization","volume":"12","author":"Li","year":"2019","journal-title":"Epigenet Chromatin"},{"key":"B29","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1186\/s12967-020-02503-9","article-title":"Genomic landscape of the immune microenvironments of brain metastases in breast cancer","volume":"18","author":"Lu","year":"2020","journal-title":"J Transl Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-009993","article-title":"Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway","volume":"13","author":"Wei","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B31","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s12885-025-13439-y","article-title":"Screening of necroptosis-related genes and evaluating the prognostic capacity, clinical value, and the effect of their copy number variations in acute myeloid leukemia","volume":"25","author":"Wen","year":"2025","journal-title":"BMC Cancer"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.951077","article-title":"Prognostic value of LECT2 and relevance to immune infiltration in hepatocellular carcinoma","volume":"13","author":"Qin","year":"2022","journal-title":"Front Genet"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1166052","article-title":"Establishment and validation of exhausted CD8+ T cell feature as a prognostic model of HCC","volume":"14","author":"Shi","year":"2023","journal-title":"Front Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1080\/02648725.2023.2191092","article-title":"The prognostic value of RHBDF2 in Pan-Cancer, and its correlation with cell Adhesion of Hepatocellular Carcinoma","volume":"40","author":"Gong","year":"2024","journal-title":"Biotechnol Genet Eng Rev"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122253","article-title":"Identification of the role of MCM6 in bladder cancer prognosis, immunotherapy response, and in vitro experimental investigation using multi-omics analysis","volume":"335","author":"Wang","year":"2023","journal-title":"Life Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.137809","article-title":"ANXA6 expression as a potential indicator of tumor diagnosis, metastasis and immunity in nasopharyngeal carcinoma","volume":"283","author":"Wang","year":"2024","journal-title":"Int J Biol Macromol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbac558","article-title":"GSCA: an integrated platform for gene set cancer analysis at genomic, pharmacogenomic and immunogenomic levels","volume":"24","author":"Liu","year":"2023","journal-title":"Brief Bioinform"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3500","article-title":"Discovering severe adverse reactions from pharmacokinetic drug-drug interactions through literature analysis and electronic health record verification","volume":"117","author":"Jeong","year":"2025","journal-title":"Clin Pharmacol Ther"},{"key":"B39","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12935-025-03715-z","article-title":"The collagen-modifying enzyme GLT25D1 is a prognostic indicator related to immunosuppression and Malignant phenotypes in hepatocellular carcinoma","volume":"25","author":"Qiu","year":"2025","journal-title":"Cancer Cell Int"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2024.156762","article-title":"The role of cellular senescence in the pathogenesis of Rheumatoid Arthritis: Focus on IL-6 as a target gene","volume":"184","author":"Xu","year":"2024","journal-title":"Cytokine"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.3c01473","article-title":"Metabolic-related gene prognostic index for predicting prognosis, immunotherapy response, and candidate drugs in ovarian cancer","volume":"64","author":"Guo","year":"2024","journal-title":"J Chem Inf Model"},{"key":"B42","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-4939-3753-0_1","article-title":"Construction of modular lentiviral vectors for effective gene expression and knockdown","volume":"1448","author":"de Bruyns","year":"2016","journal-title":"Methods Mol Biol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2005.11.007","article-title":"Western blotting","volume":"38","author":"Kurien","year":"2006","journal-title":"Methods"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.6252","article-title":"Comparison of universal genetic testing vs guideline-directed targeted testing for patients with hereditary cancer syndrome","volume":"7","author":"Samadder","year":"2021","journal-title":"JAMA Oncol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00573-2","article-title":"Immunotherapies for hepatocellular carcinoma","volume":"19","author":"Llovet","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1007\/s12672-024-01578-w","article-title":"ATP6V1C1, associated with the tumor microenvironment and mTORC1 signaling pathway, is a potential diagnostic, prognostic, and therapeutic biomarker for hepatocellular carcinoma","volume":"15","author":"Pan","year":"2024","journal-title":"Discov Oncol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.985991","article-title":"Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of shiliao decoction in the treatment of cancer-associated malnutrition","volume":"9","author":"Long","year":"2022","journal-title":"Front Nutr"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-025-01037-w","article-title":"UBE2Q2 promotes tumor progression and glycolysis of hepatocellular carcinoma through NF-\u03baB\/HIF1\u03b1 signal pathway","volume":"48","author":"Wu","year":"2025","journal-title":"Cell Oncol (Dordr)"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw5473","article-title":"Metabolic reprogramming and cancer progression","volume":"368","author":"Faubert","year":"2020","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00378-6","article-title":"Cancer metabolism: looking forward","volume":"21","author":"Mart\u00ednez-Reyes","year":"2021","journal-title":"Nat Rev Cancer"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S476273","article-title":"Aqueous extract of rhubarb promotes hepatotoxicity via facilitating PKM2-mediated aerobic glycolysis in a rat model of diethylnitrosamine-induced liver cancer","volume":"18","author":"Zhao","year":"2024","journal-title":"Drug Des Devel Ther"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2021.110098","article-title":"G6PD inhibits ferroptosis in hepatocellular carcinoma by targeting cytochrome P450 oxidoreductase","volume":"87","author":"Cao","year":"2021","journal-title":"Cell Signal"},{"key":"B53","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/s41467-019-14050-z","article-title":"Intratumoral heterogeneity and clonal evolution in liver cancer","volume":"11","author":"Losic","year":"2020","journal-title":"Nat Commun"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000029548","article-title":"Identification of G6PC as a potential prognostic biomarker in hepatocellular carcinoma based on bioinformatics analysis","volume":"101","author":"Tian","year":"2022","journal-title":"Med (Baltimore)"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfad046","article-title":"Gluconeogenesis in the kidney: in health and in chronic kidney disease","volume":"16","author":"Dalga","year":"2023","journal-title":"Clin Kidney J"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2023.11.012","article-title":"Intestinal gluconeogenesis: A translator of nutritional information needed for glycemic and emotional balance","volume":"223","author":"Gautier-Stein","year":"2024","journal-title":"Biochimie"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-14-0106-T","article-title":"Glucose-6-phosphatase is a key metabolic regulator of glioblastoma invasion","volume":"12","author":"Abbadi","year":"2014","journal-title":"Mol Cancer Res"},{"key":"B58","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1186\/s12958-022-00921-6","article-title":"G6PC indicated poor prognosis in cervical cancer and promoted cervical carcinogenesis in vitro and in vivo","volume":"20","author":"Zhu","year":"2022","journal-title":"Reprod Biol Endocrinol"},{"key":"B59","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1002\/mc.23681","article-title":"The FOXO1\/G6PC axis promotes gastric cancer progression and mediates 5-fluorouracil resistance by targeting the PI3K\/AKT\/mTOR signaling pathway","volume":"63","author":"Han","year":"2024","journal-title":"Mol Carcinog"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/S1875-5364(22)60174-2","article-title":"Influence of 6-shogaol potentiated on 5-fluorouracil treatment of liver cancer by promoting apoptosis and cell cycle arrest by regulating AKT\/mTOR\/MRP1 signaling","volume":"20","author":"Zhang","year":"2022","journal-title":"Chin J Nat Med"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.7150\/jca.97437","article-title":"DPF2 overexpression correlates with immune infiltration and dismal prognosis in hepatocellular carcinoma","volume":"15","author":"Yang","year":"2024","journal-title":"J Cancer"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.03.083","article-title":"Hepatic glucose-6-phosphatase-\u03b1 deficiency leads to metabolic reprogramming in glycogen storage disease type Ia","volume":"498","author":"Cho","year":"2018","journal-title":"Biochem Biophys Res Commun"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.11.026","article-title":"The molecular functions of hepatocyte nuclear factors - In and beyond the liver","volume":"68","author":"Lau","year":"2018","journal-title":"J Hepatol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"2753","DOI":"10.1016\/j.molcel.2023.06.028","article-title":"UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability","volume":"83","author":"Tsai","year":"2023","journal-title":"Mol Cell"},{"key":"B65","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1186\/s12967-023-04617-2","article-title":"The potential role of reprogrammed glucose metabolism: an emerging actionable codependent target in thyroid cancer","volume":"21","author":"Duan","year":"2023","journal-title":"J Transl Med"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216285","article-title":"NUSAP1-LDHA-Glycolysis-Lactate feedforward loop promotes Warburg effect and metastasis in pancreatic ductal adenocarcinoma","volume":"567","author":"Chen","year":"2023","journal-title":"Cancer Lett"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.717182","article-title":"Comprehensive analyses of glucose metabolism in glioma reveal the glioma-promoting effect of GALM","volume":"9","author":"Xu","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.21147\/j.issn.1000-9604.2019.05.07","article-title":"Phosphoglucose isomerase gene expression as a prognostic biomarker of gastric cancer","volume":"31","author":"Huang","year":"2019","journal-title":"Chin J Cancer Res"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-025-02112-1","article-title":"Metabolism-related ALDH1B1 acts as potential predictor and therapeutic target for primary gastrointestinal diffuse large B-cell lymphoma","author":"Qiao","year":"2025","journal-title":"Apoptosis"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12403","article-title":"METTL5 stabilizes c-Myc by facilitating USP5 translation to reprogram glucose metabolism and promote hepatocellular carcinoma progression","volume":"43","author":"Xia","year":"2023","journal-title":"Cancer Commun (Lond)"},{"key":"B71","doi-asserted-by":"publisher","first-page":"S2090","DOI":"10.1016\/j.jare.2025.02.035","article-title":"Long non-coding RNA LINC01532 sustains redox homeostasis and accelerates lenvatinib resistance in hepatocellular carcinoma","author":"Hu","year":"2025","journal-title":"J Adv Res"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1002\/tox.24317","article-title":"Impact of anesthesia-related genes on prognosis and tumor microenvironment in hepatocellular carcinoma: A comprehensive analysis","volume":"39","author":"Xu","year":"2024","journal-title":"Environ Toxicol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102820","article-title":"Development and validation of a prognostic classifier based on HIF-1 signaling for hepatocellular carcinoma","volume":"12","author":"Deng","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202279","article-title":"Exploration of the immune cell infiltration-related gene signature in the prognosis of melanoma","volume":"13","author":"Zeng","year":"2021","journal-title":"Aging (Albany NY)"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1431211","article-title":"Regulatory T cells and immune escape in HCC: understanding the tumor microenvironment and advancing CAR-T cell therapy","volume":"15","author":"Du","year":"2024","journal-title":"Front Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2024.07.009","article-title":"CD4+ T cells in antitumor immunity","volume":"10","author":"Montauti","year":"2024","journal-title":"Trends Cancer"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines13050496","article-title":"Harnessing dendritic cell function in hepatocellular carcinoma: advances in immunotherapy and therapeutic strategies","volume":"13","author":"Ying","year":"2025","journal-title":"Vaccines (Basel)"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-321702","article-title":"Immunotherapy for advanced hepatocellular carcinoma: a focus on special subgroups","volume":"70","author":"Pinter","year":"2021","journal-title":"Gut"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.783236","article-title":"Strategies to improve the antitumor effect of immunotherapy for hepatocellular carcinoma","volume":"12","author":"Xing","year":"2021","journal-title":"Front Immunol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/nature13848","article-title":"CEACAM1 regulates TIM-3-mediated tolerance and exhaustion","volume":"517","author":"Huang","year":"2015","journal-title":"Nature"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1623315\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T05:33:15Z","timestamp":1754026395000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1623315\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,1]]},"references-count":80,"alternative-id":["10.3389\/fimmu.2025.1623315"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1623315","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,1]]},"article-number":"1623315"}}