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一种与 EMT 相关的免疫生物标志物可作为膀胱癌预后和药物反应的预测因子。

An immune biomarker associated with EMT serves as a predictor for prognosis and drug response in bladder cancer.

机构信息

Department of Ultrasonography, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330000, China.

Second College of Clinical Medicine, Nanchang University, Nanchang, Jiangxi 330000, China.

出版信息

Aging (Albany NY). 2024 Jul 8;16(13):10813-10831. doi: 10.18632/aging.205927.

DOI:10.18632/aging.205927
PMID:38980253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11272103/
Abstract

BACKGROUND

Bladder cancer (BLCA), which develops from the upper endometrial of the bladder, is the sixth most prevalent cancer across the globe. WDHD1 (WD repeat and HMG-box DNA binding protein 1 gene) directly affects signaling, the cell cycle, and the development of the cell skeleton. Uncertainty surrounds WDHD1's function in BLCA immunity and prognosis, though.

MATERIALS AND METHODS

Using weighed gene co-expression network analysis (WGCNA), initially, we first identified 32 risk factors in genes with differential expression for this investigation. Then, using a variety of bioinformatic techniques and experimental validation, we examined the connections between WDHD1 and BLCA expression, clinical pathological traits, WDHD1-related proteins, upper-skin-intermediate conversion (EMT), immune cell immersion, convergence factors, immune markers, and drug sensitivity.

RESULT

The findings demonstrated that we constructed a 32-gene risk-predicting model where WDHD1 was elevated as a representative gene expression in BLCA and related to a range of clinical traits. Furthermore, high WDHD1 expression was a standalone predictor associated with a worse survival rate. The most commonly recruited cells and their evolutionary patterns were highlighted to better comprehend WDHD1's function in cancer. High WDHD1 expression was associated with many aspects of immunology. Finally, the study found that individuals with high expression of WDHD1 were drug-sensitive to four different broad-spectrum anti-cancer drugs.

CONCLUSION

These results describe dynamic changes in the tumor microenvironment in BLCA and provide evidence for the hypothesis that WDHD1 is a novel biomarker of tumor development. WDHD1 may therefore be a useful target for the detection and management of BLCA.

摘要

背景

膀胱癌(BLCA)起源于膀胱的上层内膜,是全球第六大常见癌症。WDHD1(WD 重复和 HMG 盒 DNA 结合蛋白 1 基因)直接影响信号转导、细胞周期和细胞骨架的发育。然而,WDHD1 在 BLCA 免疫和预后中的功能尚不确定。

材料和方法

我们首先使用加权基因共表达网络分析(WGCNA),从差异表达的基因中鉴定出 32 个风险因素。然后,我们使用多种生物信息学技术和实验验证,研究了 WDHD1 与 BLCA 表达、临床病理特征、WDHD1 相关蛋白、上皮-间质转化(EMT)、免疫细胞浸润、趋化因子、免疫标志物和药物敏感性之间的关系。

结果

研究结果表明,我们构建了一个 32 基因风险预测模型,其中 WDHD1 作为 BLCA 中代表性基因表达上调,并与一系列临床特征相关。此外,高 WDHD1 表达是一个独立的预后不良预测因子。突出显示最常招募的细胞及其进化模式,以更好地理解 WDHD1 在癌症中的功能。高 WDHD1 表达与免疫学的许多方面有关。最后,研究发现,高 WDHD1 表达的个体对四种不同的广谱抗癌药物敏感。

结论

这些结果描述了 BLCA 肿瘤微环境中的动态变化,并为 WDHD1 是肿瘤发展的新型生物标志物这一假说提供了证据。因此,WDHD1 可能是 BLCA 检测和管理的有用靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/491584e632e9/aging-16-205927-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/47c5e6b7ed03/aging-16-205927-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/e466bd388df9/aging-16-205927-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/f5b18d3c67b2/aging-16-205927-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/e902f00cec63/aging-16-205927-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/491584e632e9/aging-16-205927-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/47c5e6b7ed03/aging-16-205927-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/59189468aa32/aging-16-205927-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/2343ece0b02a/aging-16-205927-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/a878703b435d/aging-16-205927-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/e466bd388df9/aging-16-205927-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/f5b18d3c67b2/aging-16-205927-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/e902f00cec63/aging-16-205927-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/27aa/11272103/491584e632e9/aging-16-205927-g008.jpg

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本文引用的文献

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Weighted gene coexpression network analysis and machine learning reveal oncogenome associated microbiome plays an important role in tumor immunity and prognosis in pan-cancer.加权基因共表达网络分析和机器学习揭示癌基因组相关微生物组在泛癌的肿瘤免疫和预后中发挥重要作用。
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Inflammatory and interferon gene expression signatures in patients with mitochondrial disease.
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