{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:21:05Z","timestamp":1780478465691,"version":"3.54.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T00:00:00Z","timestamp":1697068800000},"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>Origin recognition complex 6 (<jats:italic>ORC6<\/jats:italic>) is one of the six highly conserved subunit proteins required for DNA replication and is essential for maintaining genome stability during cell division. Recent research shows that <jats:italic>ORC6<\/jats:italic> regulates the advancement of multiple cancers; however, it remains unclear what regulatory impact it has on the tumor immune microenvironment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Unpaired Wilcoxon rank sum and signed rank tests were used to analyze the differences in the expression of <jats:italic>ORC6<\/jats:italic> in normal tissues and corresponding tumor tissues. Multiple online databases have evaluated the genetic alterations, protein expression and localization, and clinical relevance of <jats:italic>ORC6<\/jats:italic>. To evaluate the potential prognostic impact and diagnostic significance of <jats:italic>ORC6<\/jats:italic> expression, we carried out log-rank, univariate Cox regression, and receiver operating characteristic curve analysis. The ICGC-LIRI-JP cohort, CGGA-301 cohort, CGGA-325 cohort, CGGA-693 cohort, and GSE13041 cohort were used for external validation of the study findings. The associations between <jats:italic>ORC6<\/jats:italic> expression and immune cell infiltration, immune checkpoint expression, and immunotherapy cohorts was further analyzed. To explore the functional and signaling pathways related to <jats:italic>ORC6<\/jats:italic> expression, gene set enrichment analysis was performed. To clarify the expression and function of <jats:italic>ORC6<\/jats:italic> in hepatocellular carcinoma (LIHC) and glioma, we conducted <jats:italic>in vitro<\/jats:italic> experiments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression of <jats:italic>ORC6<\/jats:italic> is upregulated in the majority of cancer types and is associated with poor patient prognosis, notably in cases of LIHC and gliomas. In addition, <jats:italic>ORC6<\/jats:italic> may be involved in multiple signaling pathways related to cancer progression and immune regulation. High expression of <jats:italic>ORC6<\/jats:italic> correlates with an immunosuppressive state in the tumor microenvironment. The results of further immunotherapy cohort analysis suggested that patients in the <jats:italic>ORC6<\/jats:italic> high-expression group benefited from immunotherapy. Inhibiting <jats:italic>ORC6<\/jats:italic> expression suppressed the proliferative and migratory abilities of LIHC and glioma cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>High expression of <jats:italic>ORC6<\/jats:italic> may be used as a biomarker to predict the poor prognosis of most tumor patients. The high expression of <jats:italic>ORC6<\/jats:italic> may be involved in the regulation of the tumor immunosuppressive environment, and it is expected to become a molecular target for inhibiting tumor progression.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1236806","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T16:58:28Z","timestamp":1697129908000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Multi-omics analysis reveals the involvement of origin recognition complex subunit 6 in tumor immune regulation and malignant 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