基于 TRPV 通道家族基因鉴定两种肺腺癌亚型的预后和免疫特征

IF 2.3 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Membrane Biology Pub Date : 2024-04-01 Epub Date: 2023-12-27 DOI:10.1007/s00232-023-00300-1
Jianhua Jiang, Pengchao Zheng, Lei Li
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引用次数: 0

摘要

肺腺癌(LUAD)是全球最致命的恶性肿瘤之一。瞬时受体电位类香草素(TRPV)通道在许多癌症中起着举足轻重的作用,但它们对肺腺癌的影响仍有待探索。本研究根据TRPV1-6基因的表达特征将LUAD样本分为两个亚型,其中LUAD亚型群2的存活率明显高于群1。随后,我们对cluster1和cluster2之间的差异表达基因(DEGs)进行了分析,发现DEGs富集于通道活性和Ca2+信号通路。我们建立了基于 DEGs 的蛋白-蛋白相互作用网络,并根据 170 个蛋白节点对应的基因,利用 Cox 回归分析构建了 LUAD 预后模型。该预后模型对患者的预后具有良好的预测能力,低风险(LR)组患者的生存率更高。根据 Cox 回归分析,风险评分被验证为一个独立的预后指标。绘制了临床适用的提名图。免疫学分析表明,低危(LR)组和高危(HR)组的免疫细胞浸润比例各不相同。免疫疗法预测表明,LR 组的 LUAD 患者更有可能从免疫检查点阻断疗法中获益。此外,我们还假设 LUAD 模型中特征基因的表达模式与肺癌治疗药物 TAS-6417 和厄洛替尼的敏感性有关。总之,我们的LUAD预后模型在预后和免疫治疗反应预测方面具有临床应用价值。
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Identification of Prognostic and Immune Characteristics of Two Lung Adenocarcinoma Subtypes Based on TRPV Channel Family Genes.

Lung adenocarcinoma (LUAD) is one of the deadliest malignant tumors worldwide. Transient receptor potential vanilloid (TRPV) channels take pivotal parts in many cancers, but their impact on LUAD remains unexplored. In this study, LUAD samples were classified into two subtypes according to the expression characteristics of TRPV1-6 genes, with LUAD subtype cluster2 exhibiting significantly higher survival rates than cluster1. Subsequently, analysis of differentially expressed genes (DEGs) was performed between cluster1 and cluster2, revealing enrichment of DEGs in channel activity and Ca2+ signaling pathways. We established a protein-protein interaction network based on DEGs and constructed a LUAD prognostic model by using Cox regression analysis based on genes corresponding to 170 protein nodes. The prognostic model demonstrated good predictive ability for patient prognosis, with higher survival rates observed in the low-risk (LR) group. The risk score was validated as an independent prognostic indicator, according to Cox regression analysis. A clinically applicable nomogram was plotted. Immunological analysis indicated that the LR and high-risk (HR) groups had varied proportions of immune cell infiltration. The immunotherapy prediction indicated that LUAD patients in LR group had a greater likelihood to benefit from immune checkpoint blockade therapy. Furthermore, we hypothesized that the expression patterns of feature genes in the LUAD model were related to the sensitivity to lung cancer therapeutic drugs TAS-6417 and Erlotinib. To sum up, our LUAD prognostic model possessed clinical applicability for prognosis and immunotherapy response prediction.

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来源期刊
Journal of Membrane Biology
Journal of Membrane Biology 生物-生化与分子生物学
CiteScore
4.80
自引率
4.20%
发文量
63
审稿时长
6-12 weeks
期刊介绍: The Journal of Membrane Biology is dedicated to publishing high-quality science related to membrane biology, biochemistry and biophysics. In particular, we welcome work that uses modern experimental or computational methods including but not limited to those with microscopy, diffraction, NMR, computer simulations, or biochemistry aimed at membrane associated or membrane embedded proteins or model membrane systems. These methods might be applied to study topics like membrane protein structure and function, membrane mediated or controlled signaling mechanisms, cell-cell communication via gap junctions, the behavior of proteins and lipids based on monolayer or bilayer systems, or genetic and regulatory mechanisms controlling membrane function. Research articles, short communications and reviews are all welcome. We also encourage authors to consider publishing ''negative'' results where experiments or simulations were well performed, but resulted in unusual or unexpected outcomes without obvious explanations. While we welcome connections to clinical studies, submissions that are primarily clinical in nature or that fail to make connections to the basic science issues of membrane structure, chemistry and function, are not appropriate for the journal. In a similar way, studies that are primarily descriptive and narratives of assays in a clinical or population study are best published in other journals. If you are not certain, it is entirely appropriate to write to us to inquire if your study is a good fit for the journal.
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