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TRAIP 作为潜在的预后生物标志物,与肺腺癌中的免疫浸润相关

英文原题:TRAIP serves as a potential prognostic biomarker and correlates with immune infiltrates in lung adenocarcinoma.

查看英文原题

TRAIP serves as a potential prognostic biomarker and correlates with immune infiltrates in lung adenocarcinoma.

PubMed 2023/07/12(内容时间) Int Immunopharmacol Q1 · IF 5.6(JCR 2025)

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研究概要

我们的研究发现 TRAIP 是 LUAD 中的致癌基因,可能成为 LUAD 潜在的预后生物标志物和有前景的治疗靶点。

研究思路结论见上方概要

肺腺癌(LUAD)是肺癌的主要类型之一,具有高发病率和死亡率。TRAF相互作用蛋白(TRAIP)是一种环型E3泛素连接酶,近年来被发现于多种癌症中发挥关键作用。然而,TRAIP在LUAD中的表达和功能仍不明确。

在本研究中,我们运用生物信息学工具及分子实验,探究了TRAIP的确切作用及其潜在机制。

通过对 UALCAN、GEPIA 和 GTEx、GEO 和 HPA 数据库的数据挖掘发现,TRAIP 在 LUAD 组织中的表达显著高于癌旁正常组织。Kaplan-Meier 曲线显示,TRAIP 高表达与较差的总生存期(OS)和无复发生存期(RFS)相关。单因素和多因素 cox 回归分析显示,TRAIP 是 LUAD 的独立危险因素。基于 TRAIP 的列线图进一步支持了 TRAIP 在 LUAD 中的预后作用。基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析表明,TRAIP 相关基因主要参与 DNA 复制、细胞周期等过程。免疫浸润分析表明,TRAIP 表达与多种免疫细胞类型的浸润密切相关,包括 B 细胞、CD8 + T 细胞、中性粒细胞和树突状细胞。此外,观察到 TRAIP 表达与TIL(肿瘤浸润淋巴细胞)(TILs)和免疫检查点分子显著相关。体外实验进一步证实,敲低 TRAIP 可抑制细胞迁移和侵袭,并减少趋化因子产生和抑制 M2 样巨噬细胞募集。最后,CMap 分析确定了 10 种可能靶向 TRAIP 的小分子化合物,为 LUAD 提供了潜在治疗方法。

展开英文摘要原文

Lung adenocarcinoma (LUAD) is one of the major types of lung cancer with high morbidity and mortality. The TRAF-interacting protein (TRAIP) is a ring-type E3 ubiquitin ligase which has been recently identified to play pivotal roles in various cancers. However, the expression and function of TRAIP in LUAD remain elusive.

In this study, we used bioinformatic tools as well as molecular experiments to explore the exact role of TRAIP and the underlying mechanism.

Data mining across the UALCAN, GEPIA and GTEx, GEO and HPA databases revealed that TRAIP was significantly overexpressed in LUAD tissues than that in adjacent normal tissues. Kaplan-Meier curve showed that high TRAIP expression was associated with poor overall survival (OS) and relapse-free survival (RFS). Univariate and multivariate cox regression analysis revealed that TRAIP was an independent risk factor in LUAD. And the TRAIP-based nomogram further supported the prognostic role of TRAIP in LUAD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that TRAIP-associated genes were mainly involved in DNA replication, cell cycle and other processes. The immune infiltration analysis indicated that TRAIP expression was tightly correlated with the infiltration of diverse immune cell types, including B cell, CD8 + T cell, neutrophil and dendritic cell. Moreover, TRAIP expression was observed to be significantly associated with tumor infiltrating lymphocytes (TILs) and immune checkpoint molecules. In vitro experiments further confirmed knockdown of TRAIP inhibited cell migration and invasion, as well as decreasing chemokine production and inhibiting M2-like macrophage recruitment. Lastly, CMap analysis identified 10 small molecule compounds that may target TRAIP, providing potential therapies for LUAD.

Collectively, our study found that TRAIP is an oncogenic gene in LUAD, which may be a potential prognostic biomarker and promising therapeutic target for LUAD.

论文信息

作者
Jing Y、Mao Z、Zhu J、Ma X、Liu H、Chen F
第一作者单位
Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.China
通讯作者单位
Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China. Electronic address: chenfengling@sjtu.edu.cn.China
期刊
International immunopharmacology2023 Sep
原文标识
PubMed 37451021 · DOI 10.1016/j.intimp.2023.110605