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FBXW 家族在预后和免疫浸润中具有潜在意义的泛癌分析

英文原题:Pan-cancer analysis of FBXW family with potential implications in prognosis and immune infiltration.

查看英文原题

Pan-cancer analysis of FBXW family with potential implications in prognosis and immune infiltration.

PubMed 2022/12/14(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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研究概要

我们的结果为指导 FBXW 家族基因在癌症中作用的治疗方向提供了有价值的策略。

研究思路结论见上方概要

含有F-box和WD重复结构域的SCF E3复合物家族(FBXW)有10个成员,负责泛素化和降解参与细胞周期调控和肿瘤发生的底物蛋白。其中,FBXW1(也称为b-TrCP1/BTRC)和FBXW7是该类别中的核心蛋白。然而,对于FBXW家族成员,尤其是FBXW1和FBXW7,在各种肿瘤类型中的贡献,仍缺乏详尽的探索。

在本研究中,我们初步分析了FBXW家族的遗传结构特征,并基于TCGA泛癌数据系统研究了它们的表达模式和临床相关性。还通过Kaplan-Meier法对FBXWs进行了生存分析。此外,我们通过Timer和xCell等免疫相关算法评估了它们的免疫浸润水平。

FBXW家族成员存在明显的遗传异质性和不同的临床特征。此外,我们通过生存分析发现FBXW家族基因可能有助于预测预后和治疗疗效。本研究还清晰阐明了FBXW家族的免疫浸润情况。结果表明,这些基因与免疫评分、免疫亚型、TIL(肿瘤浸润淋巴细胞)和免疫检查点等免疫组分密切相关。值得注意的是,作为癌基因的FBXW1和作为抑癌基因的FBXW7在免疫细胞上也表现出相反的关系。

展开英文摘要原文

The F-box and WD repeat domain containing (FBXW) family of SCF E3 complexes has 10 members that are responsible for ubiquitination and degradation of substrate proteins involved in cell cycle regulation and tumorigenesis. Among them, FBXW1 (also called b-TrCP1/BTRC) and FBXW7 are the central proteins in this category. However, there is still a lack of elaborate exploration of the contribution of FBXW family members, especially FBXW1 and FBXW7, in various tumor types.

In this present study, we preliminarily analyzed the genetic structure characteristics of the FBXW family, and systematically investigated their expression patterns and clinical correlations based on the TCGA pan-cancer data. Survival analysis of FBXWs was also conducted through the Kaplan-Meier method. In addition, we assessed their immune infiltration level through immune-related algorithms like Timer and xCell.

There were obvious genetic heterogeneity and different clinical traits in FBXW family members. Moreover, we found that FBXW family genes may be useful in predicting prognosis and therapeutic efficacy using survival analysis. In addition, the immune infiltration of FBXW family was also clearly illustrated in this study. The results showed these genes were closely involved in immune components such as immune score, immune subtypes, tumor-infiltrating lymphocytes and immune checkpoints. Notedly, FBXW1 as an oncogene and FBXW7 as a tumor suppressor gene also show opposite relationships on immune cells.

Our results provided valuable strategies to guide the therapeutic orientation concerning the role of FBXW family genes in cancer.

论文信息

作者
Huang T、OuYang X、Li J、Shi B、Shan Z、Shi Z、Yang Z
第一作者单位
School of Medicine, Xiamen University, Xiamen, China.China
通讯作者单位
Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.China
文献类型
非美国政府资助研究
期刊
Frontiers in immunology2022
原文标识
PubMed 36591289 · DOI 10.3389/fimmu.2022.1084339