P4HB在肿瘤微环境中的潜在作用及其临床预后价值：一项以肾透明细胞癌为重点的全面泛癌分析及实验验证
Potential role of P4HB in the tumor microenvironment and its clinical prognostic value: a comprehensive pan-cancer analysis and experimental validation with a focus on KIRC.
作者信息
Zhang Linxue, Li Yu-Wei, Xie Tianyi, Sun Ke, Huang Xiang, Xiong Wei, Liu Rui-Ji
机构信息
School of Materials and Energy, University of Electronic Science and Technology of China, Chengdu, 610054, China.
School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610054, Sichuan, China.
出版信息
Cancer Cell Int. 2025 Jan 3;25(1):1. doi: 10.1186/s12935-024-03575-z.
BACKGROUND
Tumor microenvironment (TME) plays a crucial role in tumor growth and metastasis. Exploring biomarkers that are significantly associated with TME can help guide individualized treatment of patients.
METHODS
We analyzed the expression and survival of P4HB in pan-cancer through the TCGA database, and verified the protein level of P4HB by the HPA database. In addition, we used the Metascape database to construct protein-protein interaction networks and the single-cell Sequencing database for functional analysis. An immune cell infiltration analysis was performed to explore the potential role of P4HB in TME. We further analyze the relationship between P4HB and immune checkpoint molecules to explore the role of P4HB in immune checkpoint blockade therapy. Finally, the oncogenic role of P4HB in RCC cells was validated using colony formation and wound healing assays.
RESULTS
RNA and protein levels of P4HB were extensively up-regulated in pan-cancer. However, high P4HB expression was associated with poor survival in KIRC. The clinical relevance analyses of P4HB suggested that high P4HB expression was associated with advanced clinical TNM stage. Moreover, multivariate cox regression analysis indicated that P4HB (HR = 1.372, 95% CI 1.047-1.681, P = 0.019) was an independent risk factor for OS in KIRC. Functional analysis revealed that P4HB is involved in hypoxia, TME and immune system processes. Our study also found that high P4HB expression was significantly correlated with elevated infiltration levels in CD8 + T cells and M2 macrophages. The results of colony formation and wound healing assays showed that knockdown of P4HB inhibited the RCC growth and migration.
CONCLUSIONS
P4HB is a specific biomarker for KIRC prognosis and is significantly associated with clinical characteristics. In addition, P4HB may play an influential role in TME and is a biomarker for ICB therapy.
背景
肿瘤微环境（TME）在肿瘤生长和转移中起关键作用。探索与TME显著相关的生物标志物有助于指导患者的个体化治疗。
方法
我们通过TCGA数据库分析了P4HB在泛癌中的表达和生存情况，并通过HPA数据库验证了P4HB的蛋白水平。此外，我们使用Metascape数据库构建蛋白质-蛋白质相互作用网络，并使用单细胞测序数据库进行功能分析。进行免疫细胞浸润分析以探索P4HB在TME中的潜在作用。我们进一步分析了P4HB与免疫检查点分子之间的关系，以探索P4HB在免疫检查点阻断治疗中的作用。最后，使用集落形成和伤口愈合试验验证了P4HB在肾透明细胞癌（RCC）细胞中的致癌作用。
结果
P4HB的RNA和蛋白水平在泛癌中广泛上调。然而，在肾透明细胞癌中，P4HB高表达与较差的生存率相关。P4HB的临床相关性分析表明，P4HB高表达与晚期临床TNM分期相关。此外，多因素cox回归分析表明，P4HB（HR = 1.372，95%CI 1.047 - 1.681，P = 0.019）是肾透明细胞癌总生存期的独立危险因素。功能分析显示，P4HB参与缺氧、TME和免疫系统过程。我们的研究还发现，P4HB高表达与CD8 + T细胞和M2巨噬细胞浸润水平升高显著相关。集落形成和伤口愈合试验结果表明，敲低P4HB可抑制肾透明细胞癌的生长和迁移。
结论
P4HB是肾透明细胞癌预后的特异性生物标志物，与临床特征显著相关。此外，P4HB可能在TME中发挥重要作用，是免疫检查点阻断治疗的生物标志物。
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