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CSE1L 整体转录组分析与膀胱癌不良预后和免疫浸润的关系及实验验证。

Integrated transcriptome analysis of CSE1L regarding poor prognosis and immune infiltration in bladder urothelial carcinoma and experimental verification.

机构信息

Department of Urology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Beijing National Day School, Beijing, China.

出版信息

Front Immunol. 2024 Oct 4;15:1449251. doi: 10.3389/fimmu.2024.1449251. eCollection 2024.

Abstract

BACKGROUND

Bladder urothelial carcinoma (BLCA) is one of the most prevalent tumors globally, with its incidence rising notably in developed countries, significantly affecting human health. CSE1L encodes a protein that is involved in various cellular processes and plays a critical role in cancer initiation and progression. However, its role in BLCA remains underexplored.

METHODS

CSE1L expression in BLCA was analyzed using TCGA data and validated by qRT-PCR and Western blot in clinical samples. Survival analysis and Cox regression models were used to evaluate its prognostic value. Functional enrichment and protein interaction analyses were performed, and immune cell infiltration was assessed using CIBERSORT. Drug sensitivity was analyzed using GDSC data. assays evaluated the effects of CSE1L knockdown on cell proliferation, migration, and invasion.

RESULTS

CSE1L was found to be significantly overexpressed in BLCA tissues compared to normal tissues. High CSE1L expression was associated with poor overall survival and unfavorable clinicopathological features. Functional enrichment analysis revealed that DEGs related to CSE1L were involved in cell cycle regulation and immune-related pathways. Immune infiltration analysis indicated a significant correlation between CSE1L expression and various immune cell types, particularly T cells and macrophages. Drug sensitivity analysis identified several chemotherapeutic agents, including MG-132, Palbociclib, and Nutlin-3a, which were more effective in the low-CSE1L expression group, while the high-CSE1L expression group showed sensitivity to drugs like S-Trityl-L-cysteine, Bleomycin, and Cisplatin. knockdown of CSE1L in BLCA cell lines inhibited cell proliferation, migration, and invasion.

CONCLUSIONS

The overexpression of CSE1L is associated with the progression and poor prognosis of bladder cancer, suggesting it could be a promising target for bladder cancer in the future.

摘要

背景

膀胱癌(BLCA)是全球最常见的肿瘤之一,其发病率在发达国家显著上升,严重影响人类健康。CSE1L 编码一种参与多种细胞过程的蛋白质,在癌症的发生和进展中起着关键作用。然而,其在 BLCA 中的作用仍未得到充分探索。

方法

使用 TCGA 数据分析 BLCA 中的 CSE1L 表达,并通过临床样本的 qRT-PCR 和 Western blot 进行验证。采用生存分析和 Cox 回归模型评估其预后价值。进行功能富集和蛋白质相互作用分析,并使用 CIBERSORT 评估免疫细胞浸润。使用 GDSC 数据分析药物敏感性。通过 实验评估 CSE1L 敲低对细胞增殖、迁移和侵袭的影响。

结果

与正常组织相比,BLCA 组织中 CSE1L 表达显著上调。高 CSE1L 表达与总生存期差和不利的临床病理特征相关。功能富集分析显示,与 CSE1L 相关的 DEGs 参与细胞周期调控和免疫相关途径。免疫浸润分析表明,CSE1L 表达与多种免疫细胞类型,特别是 T 细胞和巨噬细胞之间存在显著相关性。药物敏感性分析确定了几种化疗药物,包括 MG-132、Palbociclib 和 Nutlin-3a,在低 CSE1L 表达组中更有效,而高 CSE1L 表达组对 S-Trityl-L-cysteine、博莱霉素和顺铂等药物敏感。在 BLCA 细胞系中敲低 CSE1L 抑制了细胞增殖、迁移和侵袭。

结论

CSE1L 的过表达与膀胱癌的进展和预后不良相关,表明它可能成为未来膀胱癌有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2fc4/11486715/e5df61f0bcf2/fimmu-15-1449251-g001.jpg

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