病毒感染相关基因CDC20在肝癌预后和免疫浸润中的新作用的生物信息学和实验分析

Juanni Li, Xiaofang Zhang, Lei Yao, K. Hu
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引用次数: 0

摘要

包括HBV和HCV在内的感染病毒已被公认为诱发肝细胞癌(HCC)的主要原因。然而,HTLV-1(人类t淋巴细胞嗜型病毒)和HCC的分子研究很少。在本研究中,我们整合了多个HCC患者的公开数据集,筛选了包括CDC20在内的7个基因作为HCC中差异表达的HTLV-1感染相关基因。基于其良好的预后能力,我们选择CDC20作为进一步研究的对象。评估CDC20的表达谱、预后评估、与临床病理特征的相关性、相关信号通路的预测以及免疫调节功能。我们发现CDC20表达在肝细胞癌组织和细胞系中显著升高,且与组织学分级、病理分期、肿瘤状态和患者年龄相关。CDC20对总生存期和疾病特异性生存期具有预后价值,是一个独立的预后因素。它主要参与几个信号通路,特别是omega-羟化酶P450和环氧化酶P450信号通路。此外,CDC20的表达与几种免疫细胞(如T辅助2细胞和滤泡辅助T细胞)、免疫刺激因子(如TNFRSF18和MICB)、免疫抑制剂(如KDR和PDCD1LG2)、趋化因子(如XCL1和CCL26)以及趋化因子受体(如CCR10和CXCR3)的水平呈显著正相关。本研究首次描述了CDC20与HTLV-1感染相关性HCC的相关性。CDC20的表达和功能紊乱使其可能成为更好的病因分类、预后预测和精准医疗的生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The bioinformatics and experimental analysis of the novel roles of virus infection-associated gene CDC20 for prognosis and immune infiltration in hepatocellular carcinoma
Infection virus including HBV and HCV has been well recognized as a major cause inducing hepatocellular carcinoma (HCC). However, molecular investigations into the HTLV-1 (Human T-lymphotropic virus type-1) and HCC have been rare. In this study, we integrated several public datasets of HCC patients and filtered seven genes including CDC20 as the HTLV-1 infection-related genes which were differentially expressed in HCC. CDC20 was chosen for further investigation based on its promising prognostic power. The expression profiles, prognostic assessment, association with clinicopathologic characteristics, prediction of correlated signal pathways, and the immune-modulating function of CDC20 were assessed. We found that CDC20 expression was significantly increased in hepatocellular carcinoma tissues and cell lines, and was correlated with histologic grade, pathologic stage, tumor status, and patient age. CDC20 exhibited prognostic value on overall survival and disease specific survival and was an independent prognostic factor. It was primarily involved in several signal pathways, especially the omega-hydroxylase P450 and epoxygenase P450 signal pathways. Moreover, CDC20 expression showed significant positive associations with the levels of several immune cells such as T helper 2 cells and follicular helper T cells, immunostimulators including TNFRSF18 and MICB, immunoinhibitors including KDR and PDCD1LG2, chemokines including XCL1 and CCL26, and chemokine receptors including CCR10 and CXCR3. This study for the first time delineated the correlation of CDC20 with HTLV-1 infection-associated HCC. The disorder of expression and function of CDC20 makes it a probable biomarker for better etiological classification, prognostic prediction, and precision medicine.
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