Wang Xing, Gao Xin, Liu Airu, Qin Yan, Ni Zhi-Yu, Zhang Xiao Lan
Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Hebei Clinical Research Center for Digestive Diseases, Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Central Laboratory, Affiliated Hospital of Hebei University, Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Hebei Key Laboratory of Precise Imaging of Inflammation Related Tumors, Hebei University, Baoding, China.
PeerJ. 2024 Dec 12;12:e18538. doi: 10.7717/peerj.18538. eCollection 2024.
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.
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.
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]; < 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.
TRAF3IP3 may be as a novel and promising biomarker for prognosis prediction and immunological evaluation of HCC.
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。我们旨在阐明TRAF3IP3与HCC之间的关系，并探索TRAF3IP3在HCC中的潜在作用。
利用癌症基因组图谱（TCGA）、基因表达综合数据库（GEO）、基因型-组织表达数据库（GTEx）、KM-Plotter数据库、阿拉巴马大学伯明翰分校癌症数据分析门户（UALCAN）以及仙桃学术在线网站对TRAF3IP3进行系统分析。该分析包括mRNA表达、蛋白质表达、预后价值、富集分析以及HCC中的免疫细胞浸润情况。随后，进行免疫组织化学以评估TRAF3IP3在HCC患者癌组织和非癌组织中的表达水平。
对公共数据库的分析以及对20对样本的免疫组织化学染色证实HCC中TRAF3IP3表达降低。TCGA数据库和GSE14520均表明，如KM曲线结果所示，TRAF3IP3高表达的患者在总生存期（OS）和无进展生存期（PFI）方面预后更佳。多变量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（风险比（HR）：0.619，95%置信区间（CI）[0.399 - 0.959]；P < 0.05）。在TRAF3IP3高表达组中，各种免疫反应相关分子途径，特别是B淋巴细胞介导的途径被激活。TRAF3IP3表达水平与肿瘤浸润性CD8 + T细胞的存在显著相关。此外，免疫表型评分（IPS）与TRAF3IP3表达之间存在正相关。值得注意的是，拉帕替尼和丝裂霉素等常用化疗药物的半数最大抑制浓度（IC50）与HCC患者中TRAF3IP3的表达呈负相关。
TRAF3IP3可能是一种用于HCC预后预测和免疫评估的新型且有前景的生物标志物。
