AUTHOR=Zhu Jinfeng , Chen Qitong , Zeng Liyun , Gao Hongyu , Wu Tong , He Yeqing , Xu Jiachi , Pang Jian , Peng Jing , Deng Yueqiong , Han Yi , Yi Wenjun 

TITLE=Multi-omics analysis reveals the involvement of origin recognition complex subunit 6 in tumor immune regulation and malignant progression

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1236806

DOI=10.3389/fimmu.2023.1236806

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Origin recognition complex 6 (<italic>ORC6</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 <italic>ORC6</italic> regulates the advancement of multiple cancers; however, it remains unclear what regulatory impact it has on the tumor immune microenvironment.</p></sec><sec><title>Methods</title><p>Unpaired Wilcoxon rank sum and signed rank tests were used to analyze the differences in the expression of <italic>ORC6</italic> in normal tissues and corresponding tumor tissues. Multiple online databases have evaluated the genetic alterations, protein expression and localization, and clinical relevance of <italic>ORC6</italic>. To evaluate the potential prognostic impact and diagnostic significance of <italic>ORC6</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 <italic>ORC6</italic> expression and immune cell infiltration, immune checkpoint expression, and immunotherapy cohorts was further analyzed. To explore the functional and signaling pathways related to <italic>ORC6</italic> expression, gene set enrichment analysis was performed. To clarify the expression and function of <italic>ORC6</italic> in hepatocellular carcinoma (LIHC) and glioma, we conducted <italic>in vitro</italic> experiments.</p></sec><sec><title>Results</title><p>Expression of <italic>ORC6</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, <italic>ORC6</italic> may be involved in multiple signaling pathways related to cancer progression and immune regulation. High expression of <italic>ORC6</italic> correlates with an immunosuppressive state in the tumor microenvironment. The results of further immunotherapy cohort analysis suggested that patients in the <italic>ORC6</italic> high-expression group benefited from immunotherapy. Inhibiting <italic>ORC6</italic> expression suppressed the proliferative and migratory abilities of LIHC and glioma cells.</p></sec><sec><title>Conclusion</title><p>High expression of <italic>ORC6</italic> may be used as a biomarker to predict the poor prognosis of most tumor patients. The high expression of <italic>ORC6</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.</p></sec>