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输出蛋白家族的泛癌分析对预后、肿瘤微环境及其潜在治疗效果的影响

Impact of pan-cancer analysis of the exportins family on prognosis, the tumor microenvironment and its potential therapeutic efficacy.

作者信息

Peng Ying, Li Youheng, Wang Lingmei, Lin Shenglai, Xu Hong

机构信息

Department of Pathology, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, 518000, Guangdong, People's Republic of China.

First Clinical College of Medicine, Guangxi Medical University, Nanning, 530021, Guangxi, People's Republic of China.

出版信息

Clin Exp Med. 2024 Dec 21;25(1):18. doi: 10.1007/s10238-024-01534-6.

Abstract

This study aims to comprehensively analyze the role of the exportin (XPO) family in the development and progression of cancer. These nuclear transport proteins have been increasingly recognized for their involvement in oncogenic processes and tumor growth. We utilized updated public databases and bioinformatics tools to assess the expression levels of the XPO family and their associations with key oncological markers including patient survival, immune subtypes, tumor microenvironment, stemness scores, drug sensitivity, and DNA methylation across various cancers. Expression levels of XPO family proteins varied significantly across different cancer types, indicating cancer-specific roles. Specific XPO proteins were linked to adverse prognosis in particular cancers. Additionally, expression levels were correlated with classifications of immune subtypes and tumor purity; notably, lower expression levels were often found in tumors with elevated stromal and immune scores. A marked correlation was observed between XPO proteins and RNA stemness scores, whereas the correlation with DNA stemness scores varied. Furthermore, XPO expression levels significantly influenced cancer cell drug sensitivity and generally showed correlations with gene methylation patterns, although these correlations differed among cancer types. Our findings underscore the distinct roles of XPO family members in cancer, linking them to immune infiltration, the tumor microenvironment, and drug sensitivity. These insights not only enhance our understanding of the prognostic and therapeutic potentials of XPO proteins in cancer but also lay the groundwork for further studies into their mechanisms and applications in cancer diagnosis and treatment.

摘要

本研究旨在全面分析输出蛋白(XPO)家族在癌症发生发展过程中的作用。这些核转运蛋白因其参与致癌过程和肿瘤生长而日益受到关注。我们利用更新后的公共数据库和生物信息学工具,评估了XPO家族的表达水平及其与关键肿瘤标志物的关联,这些标志物包括患者生存率、免疫亚型、肿瘤微环境、干性评分、药物敏感性以及多种癌症中的DNA甲基化情况。XPO家族蛋白的表达水平在不同癌症类型中差异显著,表明其具有癌症特异性作用。特定的XPO蛋白与特定癌症的不良预后相关。此外,表达水平与免疫亚型分类和肿瘤纯度相关;值得注意的是,在基质和免疫评分升高的肿瘤中,往往发现较低的表达水平。XPO蛋白与RNA干性评分之间存在显著相关性,而与DNA干性评分的相关性则有所不同。此外,XPO表达水平显著影响癌细胞的药物敏感性,并且通常与基因甲基化模式相关,尽管这些相关性在不同癌症类型中有所差异。我们的研究结果强调了XPO家族成员在癌症中的独特作用,将它们与免疫浸润、肿瘤微环境和药物敏感性联系起来。这些见解不仅增进了我们对XPO蛋白在癌症中的预后和治疗潜力的理解,也为进一步研究其在癌症诊断和治疗中的机制及应用奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309b/11663167/de605a1aa2af/10238_2024_1534_Fig1_HTML.jpg

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