评估甲状腺癌的预后模型和免疫特性的昼夜节律相关基因。

IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xiuping Qiu, Gang Chen, Mei Tu
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引用次数: 0

摘要

背景:昼夜节律相关基因(CRRGs)在各种肿瘤的存活、侵袭、增殖和转移等细胞过程的调控中起着至关重要的作用。然而,它们在甲状腺癌(THCA)中的具体功能仍不确定。本研究探讨了CRRGs在THCA中的预后意义,并评估了它们作为治疗靶点的潜力。方法:分析来自癌症基因组图谱(TCGA)的临床和基因表达数据,评估CRRGs在THCA中的相关性。使用基因集变异分析(GSVA)进行体细胞突变分析、风险模型开发以及高、低风险患者组之间的比较。评估肿瘤免疫微环境特征,并使用Kaplan-Meier (K-M)生存分析数据来检查预后结果。通过体外实验对CHEK1、GHR、ID3、IDI1、MAGEL2、NLGN1、PPARGC1A、TBL1X、TF等9种CRRGs进行功能验证。结果:基于crrg的风险模型将患者分为高危组和低危组,K-M分析显示,低危组患者预后明显较差。功能分析,包括基因本体(GO)、京都基因和基因组百科全书(KEGG)和基因集富集分析(GSEA),确定了两组中与THCA相关的途径。使用单样本GSEA (ssGSEA),通过昼夜节律评分(CRscores)进一步对患者进行分类,突出了两组之间不同的免疫特征。建立临床Cox模型,并通过体外实验验证差异基因表达。结论:本研究提出了一种新的基于crrg的THCA预后模型,为患者分层提供了有价值的工具,并为优化免疫治疗策略提供了见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Evaluation of Circadian Rhythm-related Genes for Prognosis Modeling and Immune Characterization in Thyroid Cancer.

Background: Circadian rhythm-related genes (CRRGs) play a crucial role in regulating cellular processes, including survival, invasion, proliferation, and metastasis across various tumors. However, their specific function in thyroid cancer (THCA) remains uncertain. This study explores the prognostic significance of CRRGs in THCA and evaluates their potential as therapeutic targets.

Methods: Clinical and gene expression data from the Cancer Genome Atlas (TCGA) were analyzed to assess the relevance of CRRGs in THCA. Somatic mutation analysis, risk model development, and comparisons between high- and low-risk patient groups were carried out using Gene Set Variation Analysis (GSVA). Tumor immune microenvironment characteristics were evaluated, and data from Kaplan-Meier (K-M) survival analysis was used to examine prognostic outcomes. Functional validation of nine CRRGs, namely CHEK1, GHR, ID3, IDI1, MAGEL2, NLGN1, PPARGC1A, TBL1X, and TF, was conducted through in vitro experiments.

Results: The CRRG-based risk model stratified patients into high- and low-risk groups, with K-M analysis revealing that patients in the low-risk group had significantly poorer outcomes. Functional analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), identified pathways associated with THCA in both groups. Using single-sample GSEA (ssGSEA), patients were further categorized by circadian rhythm scores (CRscores), highlighting distinct immune profiles between the two groups. A clinical Cox model was developed, and differential gene expression was validated through in vitro experiments.

Conclusion: This study presents a novel CRRG-based prognostic model for THCA, providing a valuable tool for patient stratification and providing insights for optimizing immunotherapy strategies.

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来源期刊
Current medicinal chemistry
Current medicinal chemistry 医学-生化与分子生物学
CiteScore
8.60
自引率
2.40%
发文量
468
审稿时长
3 months
期刊介绍: Aims & Scope Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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