Department of Internal Medicine, West China Hospital Cancer Center Head And Neck, Sichuan University, Chengdu, China.
Department of Cancer Center Head and Neck, West China Hospital, Sichuan University, Chengdu, China.
Mol Cancer. 2022 Jul 25;21(1):153. doi: 10.1186/s12943-022-01623-8.
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.
细胞分裂周期 6（CDC6）已被证明与人类多种肿瘤的发生和发展有关。然而，它在神经胶质瘤中的作用尚不清楚，神经胶质瘤是中枢神经系统常见的原发性恶性肿瘤之一，发病率和死亡率都很高。
在本研究中，我们探讨了 CDC6 基因在泛癌症中的表达水平。此外，我们还重点研究了 CDC6 表达与胶质瘤患者的预后价值、潜在生物学功能和免疫浸润之间的关系。我们还进行了体外实验，以评估 CDC6 表达对神经胶质瘤细胞增殖、凋亡、迁移和侵袭能力的影响。
结果表明，CDC6 在多种类型的癌症中表达上调，包括神经胶质瘤。此外，CDC6 表达水平高与神经胶质瘤患者的年龄、IDH 状态、1p/19q 缺失状态、WHO 分级和组织学类型显著相关（均 P<0.05）。同时，CDC6 高表达与神经胶质瘤患者的总生存期（OS）不良相关，特别是在不同的临床亚组中。此外，单因素 Cox 分析表明，CDC6 高表达与神经胶质瘤患者的 OS 不良相关。功能富集分析表明，CDC6 主要参与与 DNA 转录和细胞因子活性相关的途径，基因集富集分析（GSEA）显示，在 CDC6 高表达的神经胶质瘤患者中，MAPK 通路、P53 通路和 NF-κB 通路存在差异富集。单样本基因集富集分析（ssGSEA）显示，神经胶质瘤中 CDC6 的表达与 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方面的作用。最后，CCK8 检测、流式细胞术和 Transwell 检测显示，沉默 CDC6 可显著抑制 U87 细胞和 U251 细胞的增殖、迁移、侵袭，并促进其凋亡（p<0.05）。
综上所述，高表达的 CDC6 可能成为一种有前途的预后标志物，与免疫浸润相关，有望成为神经胶质瘤的潜在免疫治疗靶点。
