起源识别复合物 6 (ORC6) 是 DNA 复制所需的六个高度保守的亚基蛋白之一，对于在细胞分裂过程中维持基因组稳定性至关重要。最近的研究表明，ORC6 调节多种癌症的进展；然而，其对肿瘤免疫微环境有何调节作用尚不清楚。采用不配对Wilcoxon秩和和符号秩检验分析ORC6在正常组织和相应肿瘤组织中表达的差异。多个在线数据库评估了 ORC6 的遗传改变、蛋白质表达和定位以及临床相关性。为了评估 ORC6 表达的潜在预后影响和诊断意义，我们进行了对数排序、单变量 Cox 回归和受试者工作特征曲线分析。 ICGC-LIRI-JP队列、CGGA-301队列、CGGA-325队列、CGGA-693队列和GSE13041队列用于研究结果的外部验证。进一步分析了 ORC6 表达与免疫细胞浸润、免疫检查点表达和免疫治疗队列之间的关联。为了探索与 ORC6 表达相关的功能和信号通路，进行了基因集富集分析。为了阐明 ORC6 在肝细胞癌 (LIHC) 和神经胶质瘤中的表达和功能，我们进行了体外实验。ORC6 的表达在大多数癌症类型中上调，并且与患者预后不良相关，特别是在 LIHC 和神经胶质瘤的情况下。此外，ORC6可能参与与癌症进展和免疫调节相关的多个信号通路。 ORC6 的高表达与肿瘤微环境中的免疫抑制状态相关。进一步的免疫治疗队列分析结果提示，ORC6高表达组的患者从免疫治疗中受益。抑制ORC6表达可抑制LIHC和胶质瘤细胞的增殖和迁移能力。ORC6的高表达可作为预测大多数肿瘤患者不良预后的生物标志物。 ORC6的高表达可能参与肿瘤免疫抑制环境的调节，有望成为抑制肿瘤进展的分子靶点。Copyright © 2023 Zhu, Chen, Zeng, Gau, Wu, He, Xu, Pang,彭、邓、韩、易。

Origin recognition complex 6 (ORC6) 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 ORC6 regulates the advancement of multiple cancers; however, it remains unclear what regulatory impact it has on the tumor immune microenvironment.Unpaired Wilcoxon rank sum and signed rank tests were used to analyze the differences in the expression of ORC6 in normal tissues and corresponding tumor tissues. Multiple online databases have evaluated the genetic alterations, protein expression and localization, and clinical relevance of ORC6. To evaluate the potential prognostic impact and diagnostic significance of ORC6 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 ORC6 expression and immune cell infiltration, immune checkpoint expression, and immunotherapy cohorts was further analyzed. To explore the functional and signaling pathways related to ORC6 expression, gene set enrichment analysis was performed. To clarify the expression and function of ORC6 in hepatocellular carcinoma (LIHC) and glioma, we conducted in vitro experiments.Expression of ORC6 is upregulated in the majority of cancer types and is associated with poor patient prognosis, notably in cases of LIHC and gliomas. In addition, ORC6 may be involved in multiple signaling pathways related to cancer progression and immune regulation. High expression of ORC6 correlates with an immunosuppressive state in the tumor microenvironment. The results of further immunotherapy cohort analysis suggested that patients in the ORC6 high-expression group benefited from immunotherapy. Inhibiting ORC6 expression suppressed the proliferative and migratory abilities of LIHC and glioma cells.High expression of ORC6 may be used as a biomarker to predict the poor prognosis of most tumor patients. The high expression of ORC6 may be involved in the regulation of the tumor immunosuppressive environment, and it is expected to become a molecular target for inhibiting tumor progression.Copyright © 2023 Zhu, Chen, Zeng, Gao, Wu, He, Xu, Pang, Peng, Deng, Han and Yi.