A Pan-Cancer Analysis of the Oncogenic Role of Cell Division Cycle-Associated Protein 4 (CDCA4) in Human Tumors.
A Pan-Cancer Analysis of the Oncogenic Role of Cell Division Cycle-Associated Protein 4 (CDCA4) in Human Tumors.
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细胞分裂周期相关蛋白 4 (CDCA4) 在人类肿瘤中的致癌作用的泛癌症分析
DOI：
10.3389/fimmu.2022.826337
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发表时间：
2022
影响因子：
7.3
通讯作者：
Kong W
中科院分区：
文献类型：
--
作者：
Fang H;Sheng S;Chen B;Wang J;Mao D;Han Y;Liu Y;Wang X;Gui S;Zhang T;Zhang L;Li C;Hu X;Deng W;Liu X;Xu H;Xu W;Wang X;Liu R;Kong W
从肿瘤免疫的角度阐明CDCA 4在不同癌症中的致癌作用。从TCGA和GTEX数据库获得肿瘤样品和癌旁样品中CDCA 4表达的原始数据。此外，我们在基因表达谱交互分析（GEPIA）数据库中研究了泛癌中CDCA 4的病理分期和生存分析。考克斯比例风险模型显示高CDCA 4水平与肿瘤学中的几个重要指标相关。一方面利用TIMER工具探讨CADA 4表达与肿瘤免疫浸润的相关性;另一方面基于TCGA数据库，利用CIBERSORT和ESTIMATE计算方法评价肿瘤浸润免疫细胞（TIIC）的比例以及基质和免疫成分的含量。经线性回归分析，CDCA 4的表达与抗肿瘤药物的使用也呈高度相关性。在GeneMANIA数据库中进行蛋白质-蛋白质相互作用分析，并进行富集分析，并通过使用Gene Ontology和京都基因百科全书鉴定预测的信号通路。分别详细描述了CDCA 4表达与拷贝数变异（CNV）和甲基化之间的相关性。分子生物学实验包括Western印迹、流式细胞术、EDU染色、Transwell和伤口愈合测定，以验证CDCA 4在肝细胞癌（HCC）中的促癌作用。大多数肿瘤高表达CDCA 4。CDCA 4表达升高与OS和DFS较差相关。CDCA 4表达与TITCs之间存在显著相关性。此外，TIIC的标志物表现出CDCA 4相关免疫浸润的不同模式。此外，我们还关注了CDCA 4的表达与抗肿瘤药物使用之间的关系。CDCA 4与生物学进程（BP）、细胞成分（CC）和分子功能（MF）有关。多巴胺能突触、AMPK、鞘脂、南美锥虫病、mRNA监测是与CDCA 4正、负相关基因显著富集的通路。CNV与CDCA 4表达呈正相关。甲基化与CDCA 4表达呈负相关。分子生物学实验证实了CDCA 4在HCC中的促癌作用，CDCA 4可能作为肿瘤免疫浸润和预后不良的生物标志物，为肿瘤治疗提供了新的思路。
To unravel the oncogenic role of CDCA4 in different cancers from the perspective of tumor immunity. Raw data on CDCA4 expression in tumor samples and paracancerous samples were obtained from TCGA and GTEX databases. In addition, we investigated pathological stages and the survival analysis of CDCA4 in pan-cancer across Gene Expression Profiling Interactive Analysis (GEPIA) database. Cox Proportional Hazards Model shows that high CDCA4 levels are associated with several vital indicators in oncology. On the one hand, we explored the correlation between CADA4 expression and tumor immune infiltration by the TIMER tool; On the other hand, we utilized the methods of CIBERSORT and ESTIMATE computational to evaluate the proportion of tumor infiltrating immune cells (TIIC) and the amounts of stromal and immune components based on TCGA database. The use of antineoplastic drugs and the expression of CDCA4 also showed a high correlation via linear regression. Protein–Protein Interaction analysis was performed in the GeneMANIA database, and enrichment analysis was performed and predicted signaling pathways were identified by using Gene Ontology and Kyoto Encyclopedia of Genes. The correlation between CDCA4 expression with Copy number variations (CNV) and methylation is detailed, respectively. Molecular biology experiments including Western blotting, flow cytometry, EDU staining, Transwell and Wound Healing assay to validate the cancer promoting role of CDCA4 in hepatocellular carcinoma (HCC). Most tumors highly expressed CDCA4. Elevated CDCA4 expression was associated with poor OS and DFS. There was a significant correlation between CDCA4 expression and TITCs. Moreover, markers of TIICs exhibited distinct patterns of CDCA4 associated immune infiltration. In addition, we pay attention to the association between the expression of CDCA4 and the use of the anti-tumor drugs. CDCA4 is related to biological progress (BP), cellular component (CC) and molecular function (MF). Dopaminergic Synapse, AMPK, Sphingolipid, Chagas Disease, mRNA Surveillance were significantly enriched pathways in positive and negative correlation genes with CDCA4. CNV is thought to be a positive correlation with CDCA4 expression. Conversely, methylation is negative correlation with CDCA4 expression. Molecular biology experiments confirm a cancer promoting role for CDCA4 in HCC CDCA4 may serve as a biomarker for cancer immunologic infiltration and poor prognosis, providing a new way of thinking for cancer treatment.
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GEPIA：用于癌症和正常基因表达谱和交互式分析的网络服务器。
影响因子：
14.9
作者：
Tang Z;Li C;Kang B;Gao G;Li C;Zhang Z
通讯作者：
Zhang Z
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2.3
作者：
Abdullah, JM;Jing, X;Jurecic, R
通讯作者：
Jurecic, R
影响因子：
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作者：
Chen, Chongxiang;Chen, Siliang;Li, Huan
通讯作者：
Li, Huan
影响因子：
12.3
作者：
Li B;Severson E;Pignon JC;Zhao H;Li T;Novak J;Jiang P;Shen H;Aster JC;Rodig S;Signoretti S;Liu JS;Liu XS
通讯作者：
Liu XS