PDF(Pubmed)
Abstract：
Background: Centrosomal Protein 55 (CEP55) was initially described as a main participant in the final stage of cytokinesis. Further research identified CEP55 as a cancer-testis antigen (CTA) that is aberrantly expressed in different malignancies and a cancer vaccination candidate. The current study aimed to disclose the complete expression of CEP55, its effect on various malignancy prognoses, and its role in the tumor microenvironment. Methods: Transcriptional information regarding tumor and normal tissues, as well as externally validated and protein expression data were gathered from the Cancer Genome Atlas, Genotype-Tissue Expression project, Gene Expression Omnibus, and Human Protein Atlas. We examined the effect of CEP55 on tumor prognosis using Kaplan-Meier (KM) and univariate Cox regression analyses. In addition, we investigated the connections between CEP55 expression and hallmark cancer pathways, immune cell infiltration, and immune regulator expression across malignancies. We constructed and validated a CEP55-related risk model for hepatocellular carcinoma (HCC) and explored the correlations between CEP55 expression and HCC molecular subtypes. Finally, we investigated putative small-molecule drugs targeting CEP55 using a connectivity map (CMap) database and validated them using molecular docking analysis. Findings: CEP55 was aberrantly expressed in most cancers and revealed a prognostic value for several malignancies. Cancers with high CEP55 expression showed significantly enhanced cell cycle, proliferation, and immune-related pathways. For most malignancies, elevated CEP55 expression was associated with the infiltration of myeloid-derived suppressor cells (MDSCs) and Th2 cells. In addition, CEP55 expression was linked to immunomodulators and the potential prediction of immune checkpoint inhibitor (ICI) responses, and strongly associated with distinct molecular HCC subtypes, whereby the CEP55-based nomogram performed well in predicting short- and long-term HCC survival. Finally, we used connectivity map (CMap) and molecular docking analyses to discover three candidate small-molecule drugs that could directly bind to CEP55. Conclusion: CEP55 affected the occurrence and development of various cancers and possibly the regulation of the tumor immune microenvironment. Our findings suggest that CEP55 is a potential biomarker for prognosis and a powerful biomarker for ICI efficacy prediction.
摘要：
背景：中心体蛋白55（CEP55）最初被描述为胞质分裂最后阶段的主要参与者。进一步的研究确定CEP55是一种癌症睾丸抗原（CTA），在不同的恶性肿瘤和癌症疫苗候选中异常表达。目前的研究旨在揭示CEP55的完整表达，其对各种恶性肿瘤预后的影响，以及它在肿瘤微环境中的作用。方法：关于肿瘤和正常组织的转录信息，以及外部验证和蛋白质表达数据从癌症基因组图谱中收集，基因型-组织表达项目,基因表达综合，和人类蛋白质图谱。我们使用Kaplan-Meier（KM）和单变量Cox回归分析检查了CEP55对肿瘤预后的影响。此外,我们调查了CEP55表达与标志性癌症通路之间的联系，免疫细胞浸润，和恶性肿瘤中的免疫调节表达。我们构建并验证了CEP55相关的肝细胞癌（HCC）风险模型，并探讨了CEP55表达与HCC分子亚型之间的相关性。最后,我们使用连接图(CMap)数据库研究了靶向CEP55的推定小分子药物,并使用分子对接分析对其进行了验证.研究结果：CEP55在大多数癌症中异常表达，并揭示了几种恶性肿瘤的预后价值。具有高CEP55表达的癌症显示出显著增强的细胞周期,扩散,和免疫相关途径。对于大多数恶性肿瘤，CEP55表达升高与髓源性抑制细胞(MDSC)和Th2细胞浸润相关.此外,CEP55表达与免疫调节剂和免疫检查点抑制剂（ICI）反应的潜在预测有关。并与不同的分子HCC亚型密切相关，因此，基于CEP55的列线图在预测短期和长期HCC生存率方面表现良好。最后,我们使用连接图(CMap)和分子对接分析发现了3种可直接与CEP55结合的候选小分子药物.结论:CEP55影响多种肿瘤的发生发展,可能与肿瘤免疫微环境的调节有关。我们的研究结果表明，CEP55是预后的潜在生物标志物，也是ICI疗效预测的强大生物标志物。
