{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:53:16Z","timestamp":1792687996137,"version":"4.5.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hepatocellular carcinoma (HCC) represents a highly aggressive cancer associated with substantial patient mortality. Members of the solute carrier (SLC) protein family have been implicated in facilitating tumor development and progression. However, the specific functions and relevance of SLC41A3 in the context of HCC pathogenesis are not well defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Differentially expressed SLC genes were screened from the TCGA-LIHC cohort. Prognostic analysis identified independent prognostic factors. Diagnostic and prognostic models were constructed using machine learning and LASSO regression. Multi-omics analysis was employed to assess the expression characteristics, clinical relevance, spatial heterogeneity, and correlation with immune infiltration of SLC41A3. The biological function of SLC41A3 was validated through\n                      <jats:italic>in vitro<\/jats:italic>\n                      proliferation, colony formation, migration, and invasion assays, as well as an\n                      <jats:italic>in vivo<\/jats:italic>\n                      xenograft tumor model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixty-nine SLC genes were differentially expressed in HCC, with eight identified as independent prognostic factors, including SLC41A3. The constructed diagnostic and prognostic models based on these genes demonstrated robust performance. SLC41A3 was highlighted as the most contributory feature in the diagnostic model. High expression of SLC41A3 was significantly associated with advanced clinicopathological features, poorer patient survival, specific spatial expression patterns, and altered immune cell infiltration in the tumor microenvironment. Functionally, knockdown of SLC41A3 significantly inhibited HCC cell proliferation, migration, invasion\n                      <jats:italic>in vitro<\/jats:italic>\n                      , and suppressed tumor growth\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies SLC41A3 as a novel prognostic biomarker and a promoter of HCC progression, with its function potentially linked to immune microenvironment modulation, suggesting its promise as a therapeutic target for HCC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1861310","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:08:10Z","timestamp":1780466890000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive characterization of SLC41A3 identifies it as an immune-related prognostic biomarker and therapeutic target in hepatocellular carcinoma"],"prefix":"10.3389","volume":"17","author":[{"given":"Biyan","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery, The First Affiliated Hospital (Southwest Hospital) of Army Medical University","place":["Chongqing, China"]},{"name":"Department of General Surgery, Armed Police Corps Hospital","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunfu","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of General Surgery, Armed Police Corps Hospital","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shidong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery, Zhongda Hospital Southeast University","place":["Nanjing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leida","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, The First Affiliated Hospital (Southwest Hospital) of Army Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengsheng","family":"Dai","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory for the Mechanism and Intervention of Cancer Metastasis, Chongqing University Cancer Hospital, Chongqing University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianheng","family":"Peng","sequence":"additional","affiliation":[{"name":"Health Management Center, The First Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1039\/d0cs01075h","article-title":"Gadolinium theranostics for the diagnosis and treatment of cancer","volume":"50","author":"Robertson","year":"2021","journal-title":"Chem Soc Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2023.0106","article-title":"Management of hepatocellular carcinoma in China: Seeking common grounds while reserving differences","volume":"29","author":"Yang","year":"2023","journal-title":"Clin Mol Hepatol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1792807","article-title":"TRIM25-mediated ferroptosis resistance is closely associated with poor prognosis in hepatocellular carcinoma","volume":"17","author":"Jiang","year":"2026","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.ccell.2019.08.007","article-title":"Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer","volume":"36","author":"Ma","year":"2019","journal-title":"Cancer Cell"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12345","article-title":"Tumor-associated macrophages in liver cancer: From mechanisms to therapy","volume":"42","author":"Cheng","year":"2022","journal-title":"Cancer Commun (Lond)"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-008721","article-title":"POSTN+ cancer-associated fibroblasts determine the efficacy of immunotherapy in hepatocellular carcinoma","volume":"12","author":"Wang","year":"2024","journal-title":"J Immunother Cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.09.044","article-title":"CXCL12+ tumor-associated endothelial cells promote immune resistance in hepatocellular carcinoma","volume":"82","author":"Lu","year":"2025","journal-title":"J Hepatol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4626","article-title":"SLC transporters as therapeutic targets: emerging opportunities","volume":"14","author":"Lin","year":"2015","journal-title":"Nat Rev Drug Discov"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00001.2024","article-title":"The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications","volume":"30","author":"Gyimesi","year":"2025","journal-title":"Physiol Rev"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2025.108061","article-title":"SLC transporters as metalloptotic gatekeepers in tumorigenesis: From molecular mechanisms to clinical potential","volume":"222","author":"Pan","year":"2025","journal-title":"Pharmacol Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/srep28565","article-title":"Identification of SLC41A3 as a novel player in magnesium homeostasis","volume":"6","author":"de Baaij","year":"2016","journal-title":"Sci Rep"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.01.011","article-title":"Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy","volume":"78","author":"Liu","year":"2023","journal-title":"J Hepatol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.gendis.2023.101106","article-title":"PDCD2 as a prognostic biomarker in glioma correlates with Malignant phenotype","volume":"11","author":"Dai","year":"2024","journal-title":"Genes Dis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-026-02625-6","article-title":"m6A-dependent translation of circPICALM encodes a novel metastasis-promoting oncoprotein in intrahepatic cholangiocarcinoma","volume":"25","author":"Li","year":"2026","journal-title":"Mol Cancer"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7493-1_12","article-title":"Profiling tumor infiltrating immune cells with CIBERSORT","volume":"1711","author":"Chen","year":"2018","journal-title":"Methods Mol Biol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-25-1693","article-title":"Long-chain fatty acid redistribution induced by SLC27A2 deficiency facilitates hypoxic adaptation and immunosuppression in hepatocellular carcinoma","volume":"85","author":"Fu","year":"2025","journal-title":"Cancer Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12967-025-06086-1","article-title":"Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcoma","volume":"23","author":"Liao","year":"2025","journal-title":"J Transl Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1394241","article-title":"Protein and metabolic profiles of tyrosine kinase inhibitors co-resistant liver cancer cells","volume":"15","author":"Wang","year":"2024","journal-title":"Front Pharmacol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06102-8","article-title":"Deterministic evolution and stringent selection during preneoplasia","volume":"618","author":"Karlsson","year":"2023","journal-title":"Nature"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2024.03.038","article-title":"Single-cell atlas of penile cancer reveals TP53 mutations as a driver of an aggressive phenotype, irrespective of human papillomavirus status, and provides clues for treatment personalization","volume":"86","author":"Elst","year":"2024","journal-title":"Eur Urol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-022-00659-8","article-title":"Discoidin domain receptor 1 promotes hepatocellular carcinoma progression through modulation of SLC1A5 and the mTORC1 signaling pathway","volume":"45","author":"Pan","year":"2022","journal-title":"Cell Oncol (Dordr)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"4091","DOI":"10.1038\/s41467-021-24386-0","article-title":"Dissecting spatial heterogeneity and the immune-evasion mechanism of CTCs by single-cell RNA-seq in hepatocellular carcinoma","volume":"12","author":"Sun","year":"2021","journal-title":"Nat Commun"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30036","article-title":"Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease","volume":"69","author":"Ponziani","year":"2019","journal-title":"Hepatology"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adh9940","article-title":"Integrative multiomic analysis identifies distinct molecular subtypes of NAFLD in a Chinese population","volume":"16","author":"Ding","year":"2024","journal-title":"Sci Transl Med"},{"key":"B25","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1186\/s12943-024-02049-0","article-title":"Tumor cell-intrinsic MELK enhanced CCL2-dependent immunosuppression to exacerbate hepatocarcinogenesis and confer resistance of HCC to radiotherapy","volume":"23","author":"Tang","year":"2024","journal-title":"Mol Cancer"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.02.036","article-title":"FGF19\/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2","volume":"79","author":"Xie","year":"2023","journal-title":"J Hepatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-23-3106","article-title":"Repolarization of immunosuppressive macrophages by targeting SLAMF7-regulated CCL2 signaling sensitizes hepatocellular carcinoma to immunotherapy","volume":"84","author":"Weng","year":"2024","journal-title":"Cancer Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1016\/j.cell.2017.05.035","article-title":"Landscape of infiltrating T cells in liver cancer revealed by single-cell sequencing","volume":"169","author":"Zheng","year":"2017","journal-title":"Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.ccell.2025.01.001","article-title":"Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer","volume":"43","author":"Guo","year":"2025","journal-title":"Cancer Cell"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2024-332902","article-title":"Nuclear translocation of plasma membrane protein ADCY7 potentiates T cell-mediated antitumour immunity in HCC","volume":"74","author":"Chen","year":"2024","journal-title":"Gut"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.100155","article-title":"SLC41A1 overexpression correlates with immune cell infiltration in HCC and promotes its Malignant progression","volume":"21","author":"Chen","year":"2024","journal-title":"Int J Med Sci"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.5c14528","article-title":"Engineered dendritic cell-derived vesicles for T-cell-targeted magnesium delivery and metabolic reprogramming","volume":"19","author":"Yu","year":"2025","journal-title":"ACS Nano"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.898567","article-title":"RAB42 is a potential biomarker that correlates with immune infiltration in hepatocellular carcinoma","volume":"9","author":"Peng","year":"2022","journal-title":"Front Mol Biosci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/biom13010043","article-title":"Pan-cancer analysis of the roles and driving forces of RAB42","volume":"13","author":"Zheng","year":"2022","journal-title":"Biomolecules"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.livres.2024.11.001","article-title":"Single-cell and machine learning approaches uncover intrinsic immune-evasion genes in the prognosis of hepatocellular carcinoma","volume":"8","author":"Wang","year":"2024","journal-title":"Liver Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1668627","article-title":"Serglycin's role in primary liver cancer: insights into tumor microenvironment and macrophage interaction","volume":"16","author":"Lian","year":"2025","journal-title":"Front Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1861310\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:08:11Z","timestamp":1780466891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1861310\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":36,"alternative-id":["10.3389\/fimmu.2026.1861310"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1861310","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"article-number":"1861310"}}