Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it’s role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05). In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.

中文翻译：

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CDC6 是一种预后生物标志物，与胶质瘤中的免疫浸润相关

细胞分裂周期 6 (CDC6) 已被证明与人类多发性肿瘤的发生和进展有关。然而，它在胶质瘤中的作用尚不清楚，胶质瘤是中枢神经系统常见的原发性恶性肿瘤之一，并且与高发病率和死亡率相关。在这项研究中，我们探讨了泛癌中的 CDC6 基因表达水平。此外，我们关注 CDC6 表达、其预后价值、潜在生物学功能和胶质瘤患者免疫浸润之间的关系。我们还进行了体外实验以评估 CDC6 表达对胶质瘤细胞增殖、凋亡、迁移和侵袭能力的影响。结果，CDC6 表达在包括神经胶质瘤在内的多种癌症中上调。而且，CDC6 的高表达与胶质瘤的年龄、IDH 状态、1p/19q 共缺失状态、WHO 分级和组织学类型显着相关（均 p < 0.05）。同时，高表达 CDC6 与胶质瘤患者的总生存期（OS）差有关，尤其是在不同的临床亚组中。此外，单变量 Cox 分析表明，高 CDC6 表达与胶质瘤患者较差的 OS 相关。功能富集分析表明CDC6主要参与了与DNA转录和细胞因子活性相关的通路，基因集富集分析（Gene Set Enrichment Analysis，GSEA）显示癌症中的MAPK通路、P53通路和NF-κB通路在高CDC6的胶质瘤患者中差异富集。表达。单样本基因集富集分析（ssGSEA）显示，胶质瘤中 CDC6 表达与 Th2 细胞、巨噬细胞和嗜酸性粒细胞呈正相关，与浆细胞样树突状细胞、CD8 T 细胞和 NK CD56bright 细胞呈负相关，提示其在调节肿瘤免疫中的作用。最后，CCK8测定、流式细胞仪和transwell测定表明，沉默CDC6可以显着抑制U87细胞和U251细胞的增殖、迁移、侵袭，并促进细胞凋亡（p < 0.05）。总之，高 CDC6 表达可作为预后的有希望的生物标志物，并与免疫浸润相关，是胶质瘤潜在的免疫治疗靶点。表明其在调节肿瘤免疫中的作用。最后，CCK8测定、流式细胞仪和transwell测定表明，沉默CDC6可以显着抑制U87细胞和U251细胞的增殖、迁移、侵袭，并促进细胞凋亡（p < 0.05）。总之，高 CDC6 表达可作为预后的有希望的生物标志物，并与免疫浸润相关，是胶质瘤潜在的免疫治疗靶点。表明其在调节肿瘤免疫中的作用。最后，CCK8测定、流式细胞仪和transwell测定表明，沉默CDC6可以显着抑制U87细胞和U251细胞的增殖、迁移、侵袭，并促进细胞凋亡（p < 0.05）。总之，高 CDC6 表达可作为预后的有希望的生物标志物，并与免疫浸润相关，是胶质瘤潜在的免疫治疗靶点。