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基于胃癌调节性 T 细胞相关基因的预后模型:系统构建与验证。

A prognostic model based on regulatory T-cell-related genes in gastric cancer: Systematic construction and validation.

机构信息

Department of Gastrointestinal Surgery, Jinhua Guangfu Hospital, Jinhua, China.

出版信息

Int J Exp Pathol. 2023 Oct;104(5):226-236. doi: 10.1111/iep.12487. Epub 2023 Jun 23.

DOI:10.1111/iep.12487
PMID:37350375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10500170/
Abstract

Human gastrointestinal tumours have been shown to contain massive numbers of tumour infiltrating regulatory T cells (Tregs), the presence of which are closely related to tumour immunity. This study was designed to develop new Treg-related prognostic biomarkers to monitor the prognosis of patients with gastric cancer (GC). Treg-related prognostic genes were screened from Treg-related differentially expressed genes in GC patients by using Cox regression analysis, based on which a prognostic model was constructed. Then, combined with RiskScore, survival curve, survival status assessment and ROC analysis, these genes were used to verify the accuracy of the model, whose independent prognostic ability was also evaluated. Six Treg-related prognostic genes (CHRDL1, APOC3, NPTX1, TREML4, MCEMP1, GH2) in GC were identified, and a 6-gene Treg-related prognostic model was constructed. Survival analysis revealed that patients had a higher survival rate in the low-risk group. Combining clinicopathological features, we performed univariate and multivariate regression analyses, with results establishing that the RiskScore was an independent prognostic factor. Predicted 1-, 3- and 5-year survival rates of GC patients had a good fit with the actual survival rates according to nomogram results. In addition patients in the low-risk group had higher tumour mutational burden (TMB) values. Gene Set Enrichment Analysis (GSEA) demonstrated that genes in the high-risk group were significantly enriched in pathways related to immune inflammation, tumour proliferation and migration. In general, we constructed a 6-gene Treg-associated GC prognostic model with good prediction accuracy, where RiskScore could act as an independent prognostic factor. This model is expected to provide a reference for clinicians to estimate the prognosis of GC patients.

摘要

人类胃肠道肿瘤中含有大量肿瘤浸润调节性 T 细胞(Treg),其存在与肿瘤免疫密切相关。本研究旨在开发新的 Treg 相关预后生物标志物,以监测胃癌(GC)患者的预后。通过 Cox 回归分析从 GC 患者的 Treg 相关差异表达基因中筛选 Treg 相关预后基因,在此基础上构建预后模型。然后,结合 RiskScore、生存曲线、生存状态评估和 ROC 分析,验证模型的准确性,评估其独立预后能力。鉴定出 GC 中 6 个与 Treg 相关的预后基因(CHRDL1、APOC3、NPTX1、TREML4、MCEMP1、GH2),构建了一个 6 个基因的 Treg 相关预后模型。生存分析显示,低危组患者的生存率更高。结合临床病理特征,进行单因素和多因素回归分析,结果表明 RiskScore 是一个独立的预后因素。根据列线图结果预测的 GC 患者 1、3 和 5 年生存率与实际生存率拟合良好。此外,低危组患者的肿瘤突变负荷(TMB)值更高。基因集富集分析(GSEA)表明,高危组基因在与免疫炎症、肿瘤增殖和迁移相关的途径中显著富集。总的来说,我们构建了一个具有良好预测准确性的 6 个基因 Treg 相关 GC 预后模型,其中 RiskScore 可以作为独立的预后因素。该模型有望为临床医生评估 GC 患者的预后提供参考。

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本文引用的文献

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MCEMP1 is a potential therapeutic biomarker associated with immune infiltration in advanced gastric cancer microenvironment.MCEMP1是一种与晚期胃癌微环境中的免疫浸润相关的潜在治疗生物标志物。
Gene. 2022 Oct 5;840:146760. doi: 10.1016/j.gene.2022.146760. Epub 2022 Jul 26.
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TREML4: a Potential Target for Immunotherapy of Sepsis.TREML4:脓毒症免疫治疗的潜在靶点。
Discov Med. 2021 Sep-Oct;32(166):87-92.
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Chordin-like 1 is a novel prognostic biomarker and correlative with immune cell infiltration in lung adenocarcinoma.Chordin-like 1 是肺腺癌的一种新型预后生物标志物,与免疫细胞浸润相关。
Aging (Albany NY). 2022 Jan 12;14(1):389-409. doi: 10.18632/aging.203814.
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Multiplicity of Glycosphingolipid-Enriched Microdomain-Driven Immune Signaling.糖脂富集微区驱动的免疫信号的多态性。
Int J Mol Sci. 2021 Sep 3;22(17):9565. doi: 10.3390/ijms22179565.
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High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia.东亚年轻女性管腔型乳腺癌中APOA1/C3/A4/A5改变的高患病率。
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6
Low expression of CHRDL1 and SPARCL1 predicts poor prognosis of lung adenocarcinoma based on comprehensive analysis and immunohistochemical validation.基于综合分析和免疫组化验证,CHRDL1和SPARCL1的低表达预示肺腺癌预后不良。
Cancer Cell Int. 2021 May 12;21(1):259. doi: 10.1186/s12935-021-01933-9.
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Current treatment and recent progress in gastric cancer.胃癌的当前治疗方法和最新进展。
CA Cancer J Clin. 2021 May;71(3):264-279. doi: 10.3322/caac.21657. Epub 2021 Feb 16.
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Regulatory T cells promote glioma cell stemness through TGF-β-NF-κB-IL6-STAT3 signaling.调节性 T 细胞通过 TGF-β-NF-κB-IL6-STAT3 信号通路促进神经胶质瘤细胞干性。
Cancer Immunol Immunother. 2021 Sep;70(9):2601-2616. doi: 10.1007/s00262-021-02872-0. Epub 2021 Feb 12.
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Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.《全球癌症统计数据 2020:全球 185 个国家和地区 36 种癌症的发病率和死亡率估计》。
CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4.
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Accumulation of TNFR2-expressing regulatory T cells in malignant pleural effusion of lung cancer patients is associated with poor prognosis.肺癌患者恶性胸腔积液中表达肿瘤坏死因子受体2的调节性T细胞的积累与预后不良相关。
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