研究动态
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通过单细胞和批量RNA测序分析,发现升高的CDC45表达与肾透明细胞癌患者预后不良的整体生存率以及较差的免疫反应相关。

Elevated CDC45 Expression Predicts Poorer Overall Survival Prognoses and Worse Immune Responses for Kidney Renal Clear Cell Carcinoma via Single-Cell and Bulk RNA-Sequencing.

发表日期:2023 Aug 29
作者: Xinyu Zhang, Jianhua Zhou, Yong Wang, Xing Wang, Bingye Zhu, Qianwei Xing
来源: Immunity & Ageing

摘要:

本文的主要目标是利用单细胞和批量RNA测序方法,分析CDC45在肾透明细胞癌(KIRC)中的预后和免疫学价值。通过HPA数据库、TCGA-KIRC数据集对KIRC中的CDC45表达进行评估,并通过PCR分析和单细胞RNA测序进行验证。通过单变量/多变量回归分析确认CDC45能够独立预测KIRC的预后。采用基因集富集分析(GSEA)探索KIRC中与CDC45有关的通路。此外,还研究了CDC45与免疫之间的关系。结果显示,在KIRC中CDC45的mRNA和蛋白水平表达升高。相关性分析结果显示,随着CDC45表达的增加,患者的组织学分级、临床分期和TNM分期也增加(p < 0.05)。单变量/多变量回归分析表明CDC45是KIRC的一个独立预后因子。通过GSEA筛选出与CDC45相关的七条通路。同时发现CDC45与肿瘤突变负荷(TMB)和微卫星不稳定性(MSI)相关,但与肿瘤新抗原负荷(TNB)无关。在免疫方面,CDC45与肿瘤微环境、免疫细胞浸润和免疫检查点相关。此外,低CDC45表达与免疫治疗的良好反应有关。单细胞RNA测序显示CDC45在T细胞中表达差异显著(p < 0.05)。CDC45显示出作为KIRC的预后生物标志物和治疗靶点的潜力。同时,CDC45低表达组对免疫治疗更敏感。© 2023. 作者。
The main objective of this paper is to analyze the prognostic and immunological value of CDC45 in kidney renal clear cell carcinoma (KIRC) using single-cell and bulk RNA-sequencing approaches. The expression of CDC45 in KIRC was evaluated by the HPA database, the TCGA-KIRC dataset and verified by PCR analysis and single-cell RNA-sequencing. The ability of CDC45 to independently predict prognosis in KIRC was confirmed by univariate/multivariate regression analysis. Gene set enrichment analysis (GSEA) was employed to explore CDC45-related pathways in KIRC. In addition, Relationships between CDC45 and immunity were also examined. Elevated CDC45 expression in KIRC was demonstrated at mRNA and protein levels. The results of the correlation analysis showed that as CDC45 expression increased, so did the histological grade, clinical stage, and TNM stage of the patients (p < 0.05). Univariate/multivariate regression analysis suggested CDC45 as an independent prognostic factor for KIRC. Seven pathways related to CDC45 were screened through GSEA. Meanwhile, we found that CDC45 was correlated with tumor mutational burden (TMB) and microsatellite instability (MSI) but not tumor neoantigen burden (TNB). Regarding immunity, CDC45 exhibited correlations with the tumor microenvironment, immune cell infiltration, and immune checkpoints. Besides, low CDC45 expression was shown to be associated with a better response to immunotherapy. Single-cell RNA-sequencing revealed that CDC45 was differently expressed in T cells (p < 0.05). CDC45 showed potential as a prognostic biomarker and therapeutic target for KIRC. Meanwhile, the CDC45 low expression group was more sensitive to immunotherapy.© 2023. The Author(s).