Study of TRAF3IP3 for prognosis and immune infiltration in hepatocellular carcinoma.

IF 2.4 3区生物学 Q2 MULTIDISCIPLINARY SCIENCES PeerJ Pub Date : 2024-12-12 eCollection Date: 2024-01-01 DOI:10.7717/peerj.18538

Xing Wang, Xin Gao, Airu Liu, Yan Qin, Zhi-Yu Ni, Xiao Lan Zhang

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Abstract

Background: Tumor necrosis factor receptor-associated factor 3 (TRAF3)-interacting protein 3 (TRAF3IP3) expressed in various tumor cell. However, its role in hepatocellular carcinoma (HCC) was unclear. We aimed to demonstrate the relationship between TRAF3IP3 and HCC and explore the potential role of TRAF3IP3 in HCC.

Methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Genotype-Tissue Expression (GTEx), KM-Plotter, University of Alabama at Birmingham Cancer data analysis Portal (UALCAN), and Xiantao Academic Online Website were utilized for the systematic analysis of TRAF3IP3. This analysis included mRNA expression, protein expression, prognostic value, enrichment analysis, and immune cell infiltration in HCC. Subsequently, immunohistochemistry was performed to assess the expression levels of TRAF3IP3 in both cancer and non-cancer tissues of patients with HCC.

Results: Analysis of public databases and immunohistochemical staining on 20 pairs of samples confirmed a decrease in TRAF3IP3 expression in HCC. Both the TCGA database and GSE14520 indicated that patients with high TRAF3IP3 expression had a more favorable prognosis in terms of overall survival (OS) and progression-free interval (PFI), as shown by KM curve results. Multivariate Cox regression analysis further demonstrated that high TRAF3IP3 expression was an independent protective factor for HCC prognosis (hazard ratio (HR): 0.619, 95% confidence interval (CI) [0.399-0.959]; p < 0.05). In the high TRAF3IP3 expression group, various immune response-related molecular pathways, particularly B lymphocyte-mediated pathways, were activated. The level of TRAF3IP3 expression showed a significant correlation with the presence of tumor-infiltrating CD8+ T cells. Additionally, a positive correlation was observed between immunophenoscore (IPS) and TRAF3IP3 expression. Notably, the half-maximal inhibitory concentration (IC50) of commonly used chemotherapeutic drugs, such as lapatinib and mitomycin, was inversely associated with TRAF3IP3 expression in HCC patients.

Conclusion: TRAF3IP3 may be as a novel and promising biomarker for prognosis prediction and immunological evaluation of HCC.

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研究 TRAF3IP3 对肝细胞癌预后和免疫浸润的影响

背景：肿瘤坏死因子受体相关因子3 （TRAF3）相互作用蛋白3 （TRAF3IP3）在多种肿瘤细胞中表达。然而，其在肝细胞癌（HCC）中的作用尚不清楚。我们旨在证明TRAF3IP3与HCC之间的关系，并探讨TRAF3IP3在HCC中的潜在作用。方法：利用癌症基因组图谱（TCGA）、基因表达图谱（GEO）、基因型-组织表达图谱（GTEx）、KM-Plotter、阿拉巴马大学伯明翰分校癌症数据分析门户网站（UALCAN）和仙桃学术在线网站对TRAF3IP3进行系统分析。该分析包括mRNA表达、蛋白表达、预后价值、富集分析和免疫细胞浸润。随后，采用免疫组化方法评估TRAF3IP3在HCC患者癌组织和非癌组织中的表达水平。结果：对20对样本进行公共数据库分析和免疫组化染色，证实HCC中TRAF3IP3表达降低。TCGA数据库和GSE14520均显示，KM曲线结果显示，TRAF3IP3高表达的患者在总生存期（OS）和无进展间期（PFI）方面预后更有利。多因素Cox回归分析进一步表明，TRAF3IP3高表达是HCC预后的独立保护因素(危险比（HR）： 0.619, 95%可信区间（CI） [0.399 ~ 0.959]；P < 0.05)。在TRAF3IP3高表达组，各种免疫应答相关的分子通路，特别是B淋巴细胞介导的通路被激活。TRAF3IP3表达水平与肿瘤浸润性CD8+ T细胞存在显著相关。此外，免疫表型评分（IPS）与TRAF3IP3表达呈正相关。值得注意的是，常用化疗药物如拉帕替尼和丝裂霉素的半最大抑制浓度（IC50）与HCC患者中TRAF3IP3的表达呈负相关。结论：TRAF3IP3可能作为一种新的、有前景的HCC预后预测和免疫学评价生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

PeerJ MULTIDISCIPLINARY SCIENCES-

CiteScore

4.70

自引率

3.70%

发文量

1665

审稿时长

10 weeks

期刊介绍： PeerJ is an open access peer-reviewed scientific journal covering research in the biological and medical sciences. At PeerJ, authors take out a lifetime publication plan (for as little as $99) which allows them to publish articles in the journal for free, forever. PeerJ has 5 Nobel Prize Winners on the Board; they have won several industry and media awards; and they are widely recognized as being one of the most interesting recent developments in academic publishing.