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WD 重复结构域 43 作为新的预测指标及其在泛癌中与肿瘤免疫细胞浸润的关联

英文原题:WD repeat domain 43 as a new predictive indicator and its connection with tumor immune cell infiltration in pan-cancer.

PubMed 2024/08/02(内容时间) Medicine (Baltimore) Q2 · IF 2(JCR 2025)

研究概要

我们对WDR43在多种癌症类型中的临床特征、肿瘤发展各阶段、免疫浸润、基因突变及功能富集分析进行了全面研究。这项研究为WDR43在临床治疗中的重要性和作用提供了有价值的见解。

研究思路结论见上方概要

WD重复域43(WDR43)是一种编码WD重复序列的蛋白质组分,参与核糖体生物发生。然而,关于WDR43在癌症预后和免疫调节中的作用知之甚少。

在这项研究中,我们利用癌症基因组图谱、基因型-组织表达数据库和人类蛋白质图谱分析了WDR43在泛癌中的表达及预后意义。我们还使用免疫组织化学方法检测了48例肝细胞癌(LIHC)及癌旁组织中WDR43的差异表达。此外,我们通过生物信息学方法研究了WDR43与临床特征、基因改变、肿瘤突变负荷、微卫星不稳定性、错配修复、肿瘤微环境、免疫浸润细胞和免疫相关基因之间的相关性。进行了基因集富集分析,并确定了潜在的生物学机制。

免疫组化染色显示,在48例LIHC患者中WDR43过表达。WDR43上调与不良预后相关,包括LIHC、子宫体子宫内膜癌、头颈部鳞状细胞癌和胰腺腺癌等多种癌症的总生存期。WDR43的差异表达与微卫星不稳定性、错配修复和免疫细胞浸润显著相关。基因本体论注释分析显示,这些基因在免疫相关功能中显著富集,包括免疫反应、免疫调节和信号通路。

展开英文摘要原文

BACKGROUND: WD repeat domain 43 (WDR43) is a protein component that encodes WD-repeats and is involved in ribosome biogenesis. However, little is known about the role of WDR43 in cancer prognosis and immune modulation. METHODS: In this study, we analyzed the expression and prognostic significance of WDR43 in pan-cancer using the Cancer Genome Atlas, the Genotype-Tissue Expression, and the Human Protein Atlas. We also examined the differential expression of WDR43 in liver hepatocellular carcinoma (LIHC) and adjacent tissues of 48 patients using immunohistochemistry. Additionally, we investigated the correlation between WDR43 and clinical characteristics, gene alterations, tumor mutation burden, microsatellite instability, mismatch repair, tumor microenvironment, immune infiltrating cells, and immune-related genes using bioinformatics methods. Gene set enrichment analysis was conducted, and potential biological mechanisms were identified. RESULTS: Immunohistochemistry staining showed that WDR43 was overexpressed in LIHC among 48 patients. Upregulation of WDR43 was associated with unfavorable prognosis, including overall survival in various types of cancer such as LIHC, uterine corpus endometrial cancer, head and neck squamous cell carcinoma, and pancreatic adenocarcinoma. Differential expression of WDR43 was significantly correlated with microsatellite instability, mismatch repair, and immune cell infiltration. Gene ontology annotation analysis revealed that these genes were significantly enriched in immune-related functions, including immune response, immune regulation, and signaling pathways. CONCLUSION: We conducted a thorough investigation of the clinical features, phases of tumor development, immune infiltration, gene mutation, and functional enrichment analysis of WDR43 in various types of cancer. This research offers valuable insight into the significance and function of WDR43 in clinical therapy.

论文信息

作者
Yang X、Luo T、Liu Z、Liu J、Yang Z
第一作者单位
Department of Digestive Endoscopy, General Hospital of Northern Theater Command, Shenyang, China.China
期刊
Medicine2024 Aug 2
原文标识
PubMed 39093744 · DOI 10.1097/MD.0000000000039153