The Second Affiliated Hospital of Guangzhou Medical University, 250 Changgang East Road, Haizhu District, Guangzhou City, Guangdong Province, China.
Mol Genet Genomics. 2024 Sep 6;299(1):86. doi: 10.1007/s00438-024-02170-1.
Cholangiocarcinoma (CCA) is a heterogeneous and aggressive malignancy with limited therapeutic options and poor prognosis. The identification of reliable prognostic biomarkers and a deeper understanding of the molecular subtypes are critical for the development of targeted therapies and improvement of patient outcomes. This study aims to uncover oxidative stress-related genes (ORGs) in CCA and develop a prognostic risk model using comprehensive transcriptomic analysis from The Cancer Genome Atlas (TCGA). Through LASSO regression analysis, we identified prognosis-related ORGs and constructed a prognostic signature consisting of six ORGs. This signature demonstrated strong predictive performance in survival analysis and ROC curve assessment. Functional enrichment and GSEA analyses revealed significant enrichment of immune-related pathways among different risk groups. GSVA analysis indicated reduced activity in inflammation and oxidative stress pathways in the high-risk subgroup, and xCell results showed lower immune cell infiltration levels in this group. Additionally, immune checkpoint genes and immune-related pathways were downregulated in the high-risk subgroup. Our research has developed a unique prognostic model focusing on oxidative stress, enabling accurate forecasting of patient outcomes and providing crucial insights and recommendations for the prognosis of individuals with CCA. Future studies should aim to validate these findings in clinical settings and further explore therapeutic targets within oxidative stress pathways.
胆管癌（CCA）是一种具有异质性和侵袭性的恶性肿瘤，治疗选择有限，预后较差。鉴定可靠的预后生物标志物和深入了解分子亚型对于开发靶向治疗和改善患者预后至关重要。本研究旨在通过全面的转录组分析从癌症基因组图谱（TCGA）中发现与氧化应激相关的基因（ORGs），并开发一个预后风险模型。通过 LASSO 回归分析，我们确定了与预后相关的 ORGs，并构建了一个由六个 ORGs 组成的预后特征。该特征在生存分析和 ROC 曲线评估中表现出很强的预测性能。功能富集和 GSEA 分析表明，不同风险组之间存在显著的免疫相关途径富集。GSVA 分析表明，高危亚组中炎症和氧化应激途径的活性降低，xCell 结果表明该组中免疫细胞浸润水平较低。此外，免疫检查点基因和免疫相关途径在高危亚组中下调。我们的研究开发了一种独特的以氧化应激为重点的预后模型，能够准确预测患者的预后，并为 CCA 患者的预后提供重要的见解和建议。未来的研究应旨在在临床环境中验证这些发现，并进一步探索氧化应激途径中的治疗靶点。
