A study on construction of a prognosis model for liver cancer based on analgesic targets and screening therapeutic drugs.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2024-07-01 Epub Date: 2024-05-28 DOI:10.1007/s13258-024-01515-9
Xueyan Jiang, Yaodong Ping, Yuan Chen, Benben Zhu, Rong Fu, Yiwei Hao, Lei Fan
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引用次数: 0

Abstract

Background: Liver cancer is one of the most malignant liver diseases in the world, and the 5-year survival rate of such patients is low. Analgesics are often used to cure pain prevalent in liver cancer. The expression changes and clinical significance of the analgesic targets (ATs) in liver cancer have not been deeply understood.

Objective: The purpose of this study is to clarify the expression pattern of ATs gene in liver cancer and its clinical significance. Through the comprehensive analysis of transcriptome data and clinical parameters, the prognosis model related to ATs gene is established, and the drug information sensitive to ATs is mined.

Methods: The study primarily utilized transcriptomic data and clinical information from liver cancer patients sourced from The Cancer Genome Atlas (TCGA) database. These data were employed to analyze the expression of ATs, conduct survival analysis, gene set variation analysis (GSVA), immune cell infiltration analysis, establish a prognostic model, and perform other bioinformatic analyses. Additionally, data from liver cancer patients in the International Cancer Genome Consortium (ICGC) were utilized to validate the accuracy of the model. Furthermore, the impact of analgesics on key genes in the prognostic model was assessed using data from the Comparative Toxicogenomics Database (CTD).

Results: The study investigated the differential expression of 58 ATs genes in liver cancer compared to normal tissues. Patients were stratified based on ATs expression, revealing varied survival outcomes. Functional enrichment analysis highlighted distinctions in spindle organization, centrosome, and spindle microtubule functions. Prognostic modeling identified low TP53 expression as protective, while elevated CCNA2, NEU1, and HTR2C levels posed risks. Commonly used analgesics, including acetaminophen and others, were found to influence the expression of these genes. These findings provide insights into potential therapeutic strategies for liver cancer and shed light on the molecular mechanisms underlying its progression.

Conclusions: The collective analysis of gene signatures associated with ATs suggests their potential as prognostic predictors in hepatocellular carcinoma patients. These findings not only offer insights into cancer therapy but also provide novel avenues for the development of indications for analgesics.

Abstract Image

基于镇痛靶点和治疗药物筛选的肝癌预后模型构建研究。
背景:肝癌是世界上恶性程度最高的肝病之一,此类患者的 5 年生存率很低。镇痛药通常用于治疗肝癌患者的疼痛。肝癌中镇痛靶点(ATs)的表达变化和临床意义尚未得到深入了解:本研究旨在阐明肝癌中镇痛靶点(ATs)基因的表达模式及其临床意义。通过对转录组数据和临床指标的综合分析,建立与ATs基因相关的预后模型,挖掘对ATs敏感的药物信息:研究主要利用了来自癌症基因组图谱(TCGA)数据库的肝癌患者转录组数据和临床信息。这些数据被用来分析ATs的表达,进行生存分析、基因组变异分析(GSVA)、免疫细胞浸润分析,建立预后模型,以及进行其他生物信息学分析。此外,还利用国际癌症基因组联盟(ICGC)中肝癌患者的数据来验证模型的准确性。此外,还利用比较毒物基因组学数据库(CTD)的数据评估了镇痛药对预后模型中关键基因的影响:研究调查了肝癌中58个ATs基因与正常组织相比的表达差异。根据ATs的表达对患者进行了分层,发现了不同的生存结果。功能富集分析强调了纺锤体组织、中心体和纺锤体微管功能的差异。预后建模发现,TP53的低表达具有保护作用,而CCNA2、NEU1和HTR2C水平的升高则具有风险。研究发现,对乙酰氨基酚等常用镇痛药会影响这些基因的表达。这些发现为肝癌的潜在治疗策略提供了见解,并揭示了肝癌进展的分子机制:与ATs相关的基因特征的集体分析表明,它们有可能成为肝细胞癌患者的预后预测因子。这些发现不仅为癌症治疗提供了启示,还为开发镇痛药的适应症提供了新途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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