Bioinformatics analysis identifies WNK1 gene as a potential biomarker for cholangiocarcinoma diagnosis and immune infiltration

IF 3.5 Q3 Biochemistry, Genetics and Molecular Biology Journal of Genetic Engineering and Biotechnology Pub Date : 2024-09-27 DOI:10.1016/j.jgeb.2024.100426
Qi Sun , Xianli Lei , Xiangrong Meng , Caijun Zha , Lei Yan , Wenjing Zhang
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Abstract

Background

Cholangiocarcinoma (CHOL) is a malignant epithelial carcinoma of the digestive system with poor prognosis and high mortality. WNK lysine deficient protein kinase 1 (WNK1) is known to be associated with tumorigenesis in various cancers. However, the relationship between WNK1 and CHOL development, as well as the potential mechanisms involved, remains poorly understood.

Methods

Microarray datasets of CHOL (GSE22633 and GSE32879) were retrieved from the Gene Expression Omnibus (GEO) database. Functional enrichment and immunoinfiltration analyses were performed for genes co-expressed with WNK1. GraphPad Prism 9 was utilized for statistical data analysis and the construction of receiver operating characteristic (ROC) curves. The impact of WNK1 on the CHOL tumor microenvironment was analyzed using Tumor Immune Estimation Resource (TIMER), Venn diagrams, STRING, and TISIDB database for information on WNK1-related chemokines and chemokine receptors. Protein-protein interaction (PPI) networks were used to predict transcription factors and microRNAs interacting with WNK1 and the associated hub genes.

Results

Differential expression of WNK1 was observed between CHOL and normal samples, suggesting its diagnostic value. Functional analysis showed that WNK1 and its associated genes were primarily enriched in pathways such as leukocyte transendothelial migration and chemokine signaling. Neutrophils were the only type of infiltrating immune cells associated with WNK1 in the CHOL tumor microenvironment (TME). VEGFA and ALB were identified as hub genes, and X-C motif chemokine receptor 1 (XCR1) and C-X-C motif chemokine ligand 5 (CXCL5) were identified as core chemokines and chemokine receptors related to WNK1 and neutrophil infiltration in CHOL.

Conclusions

Based on network analysis and the summary of previous studies, it was proposed that CHOL tumor cells secrete CXCL5, leading to neutrophil recruitment to the tumor microenvironment. Vascular endothelial growth factor A (VEGFA) released by the infiltrating neutrophils is suggested to promote overexpression of WNK1 by tumor cells, activating the VEGFA downstream pathway to promote angiogenesis and tumor progression.
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生物信息学分析发现 WNK1 基因是胆管癌诊断和免疫浸润的潜在生物标志物
背景胆管癌(Cholangiocarcinoma,CHOL)是一种预后差、死亡率高的消化系统恶性上皮癌。众所周知,WNK 赖氨酸缺陷蛋白激酶 1(WNK1)与多种癌症的肿瘤发生有关。方法从基因表达总库(Gene Expression Omnibus,GEO)数据库中检索 CHOL 的微阵列数据集(GSE22633 和 GSE32879)。对与 WNK1 共表达的基因进行了功能富集和免疫渗透分析。使用 GraphPad Prism 9 进行数据统计分析并构建接收者操作特征曲线(ROC)。利用肿瘤免疫估算资源(TIMER)、维恩图、STRING和TISIDB数据库中与WNK1相关的趋化因子和趋化因子受体信息,分析了WNK1对CHOL肿瘤微环境的影响。结果观察到WNK1在CHOL和正常样本之间有差异表达,表明其具有诊断价值。功能分析显示,WNK1及其相关基因主要富集在白细胞跨内皮迁移和趋化因子信号转导等通路中。在CHOL肿瘤微环境(TME)中,中性粒细胞是唯一一种与WNK1相关的浸润免疫细胞。VEGFA和ALB被确定为中枢基因,X-C动因趋化因子受体1(XCR1)和C-X-C动因趋化因子配体5(CXCL5)被确定为与WNK1和中性粒细胞浸润有关的核心趋化因子和趋化因子受体。浸润的中性粒细胞释放的血管内皮生长因子 A(VEGFA)可促进肿瘤细胞过度表达 WNK1,激活 VEGFA 下游通路,促进血管生成和肿瘤进展。
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来源期刊
Journal of Genetic Engineering and Biotechnology
Journal of Genetic Engineering and Biotechnology Biochemistry, Genetics and Molecular Biology-Biotechnology
CiteScore
5.70
自引率
5.70%
发文量
159
审稿时长
16 weeks
期刊介绍: Journal of genetic engineering and biotechnology is devoted to rapid publication of full-length research papers that leads to significant contribution in advancing knowledge in genetic engineering and biotechnology and provide novel perspectives in this research area. JGEB includes all major themes related to genetic engineering and recombinant DNA. The area of interest of JGEB includes but not restricted to: •Plant genetics •Animal genetics •Bacterial enzymes •Agricultural Biotechnology, •Biochemistry, •Biophysics, •Bioinformatics, •Environmental Biotechnology, •Industrial Biotechnology, •Microbial biotechnology, •Medical Biotechnology, •Bioenergy, Biosafety, •Biosecurity, •Bioethics, •GMOS, •Genomic, •Proteomic JGEB accepts
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