鉴定胆管癌预后和免疫微环境的新型杯突相关基因

IF 2.7 4区 医学 Q3 ONCOLOGY
Qiang Liu, Jianpeng Zhu, Zhicheng Huang, Xiaofeng Zhang, Jianfeng Yang
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引用次数: 0

摘要

背景杯状细胞增多症是一种新型的介导细胞死亡,与多种癌症的进展密切相关,并被认为是一种潜在的治疗靶点。方法基于独立的 mRNA 和蛋白质数据集,对 146 个杯突症相关基因和临床信息进行了系统分析,以阐明杯突症相关基因的潜在机制和预后预测价值。结果表明,10个杯状细胞增多症相关基因对胆管癌预后的影响与患者的生存率显著相关。结果首先,10个杯弓蛇影相关基因特征(ADAM9、ADAM17、ALB、AQP1、CDK1、MT2A、PAM、SOD3、STEAP3和TMPRSS6)对胆管癌的总生存率有很好的预测作用。在转录组和蛋白质队列中,低杯突变组的预后明显优于高杯突变组。其次,根据CIBERSORTx和EPIC分析,与高危组和低危组相比,两组显示出不同的肿瘤微环境,内皮细胞比例降低,癌症相关成纤维细胞水平升高。第三,两组患者对化疗药物和免疫检查点的敏感性存在明显差异。最后,在复制 10 个基因的表达模式时,这些结果得到了定量实时聚合酶链反应结果的验证,验证了胆管癌中目标基因的异常表达模式。 结论总之,我们建立并验证了一个有效的预后模型,该模型可根据 10 个杯突症相关基因的分子或蛋白质特征将胆管癌患者分为 2 个异质性杯突症亚型。这些发现为揭示分子特征和定义亚组提供了潜在的益处,可改善胆管癌患者的早期诊断和个体化治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of Novel Cuproptosis-Related Genes Mediating the Prognosis and Immune Microenvironment in Cholangiocarcinoma
BackgroundCuproptosis is a novel type of mediated cell death strongly associated with the progression of several cancers and has been implicated as a potential therapeutic target. However, the role of cuproptosis in cholangiocarcinoma for prognostic prediction, subgroup classification, and therapeutic strategies remains largely unknown.MethodsA systematic analysis was conducted among 146 cuproptosis-related genes and clinical information based on independent mRNA and protein datasets to elucidate the potential mechanisms and prognostic prediction value of cuproptosis-related genes. A 10-cuproptosis-related gene prediction model was constructed, and its effects on cholangiocarcinoma prognosis were significantly connected to poor patient survival. Additionally, the expression patterns of our model included genes that were validated with several cholangiocarcinoma cancer cell lines and a normal biliary epithelial cell line.ResultsFirst, a 10-cuproptosis-related gene signature ( ADAM9, ADAM17, ALB, AQP1, CDK1, MT2A, PAM, SOD3, STEAP3, and TMPRSS6) displayed excellent predictive performance for the overall survival of cholangiocarcinoma. The low-cuproptosis group had a significantly better prognosis than the high-cuproptosis group with transcriptome and protein cohorts. Second, compared with the high-risk and low-risk groups, the 2 groups displayed distinct tumor microenvironments, reduced proportions of endothelial cells, and increased levels of cancer-associated fibroblasts based on CIBERSORTx and EPIC analyses. Third, patients’ sensitivities to chemotherapeutic drugs and immune checkpoints revealed distinctive differences between the 2 groups. Finally, in replicating the expression patterns of the 10 genes, these results were validated with quantitative real-time polymerase chain reaction results validating the abnormal expression pattern of the target genes in cholangiocarcinoma.ConclusionsCollectively, we established and verified an effective prognostic model that could separate cholangiocarcinoma patients into 2 heterogeneous cuproptosis subtypes based on the molecular or protein characteristics of 10 cuproptosis-related genes. These findings may provide potential benefits for unveiling molecular characteristics and defining subgroups could improve the early diagnosis and individualized treatment of cholangiocarcinoma patients.
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来源期刊
CiteScore
4.40
自引率
0.00%
发文量
202
审稿时长
2 months
期刊介绍: Technology in Cancer Research & Treatment (TCRT) is a JCR-ranked, broad-spectrum, open access, peer-reviewed publication whose aim is to provide researchers and clinicians with a platform to share and discuss developments in the prevention, diagnosis, treatment, and monitoring of cancer.
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