WD 重复结构域 43 作为一种新的预测指标及其与泛癌种肿瘤免疫细胞浸润的关系。

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

机构信息

Department of Digestive Endoscopy, General Hospital of Northern Theater Command, Shenyang, China.

出版信息

Medicine (Baltimore). 2024 Aug 2;103(31):e39153. doi: 10.1097/MD.0000000000039153.

DOI:10.1097/MD.0000000000039153

PMID:39093744

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11296459/

Abstract

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.

摘要

背景

WD 重复结构域 43（WDR43）是一种蛋白质成分，编码 WD 重复序列，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。

方法

本研究利用癌症基因组图谱、基因-组织表达和人类蛋白质图谱分析了 WDR43 在泛癌中的表达及预后意义。我们还通过免疫组织化学检查了 48 例肝癌患者的肝组织和癌旁组织中 WDR43 的差异表达。此外，我们还利用生物信息学方法研究了 WDR43 与临床特征、基因改变、肿瘤突变负担、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。

结果

免疫组织化学染色显示，48 例肝癌患者中 WDR43 在肝癌中过表达。WDR43 的上调与不良预后相关，包括各种癌症的总生存期，如肝癌、子宫体子宫内膜癌、头颈部鳞状细胞癌和胰腺腺癌。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。基因本体注释分析表明，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。