Peking University Cancer Hospital Inner Mongolia Hospital Pharmacy Department, Hohhot, Inner Mongolia, China.
Department of Pharmacy, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital & Institute, Beijing, China.
Genes Genomics. 2024 Jul;46(7):831-850. doi: 10.1007/s13258-024-01515-9. Epub 2024 May 28.
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.
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.
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).
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.
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.
肝癌是世界上最恶性的肝脏疾病之一,此类患者的 5 年生存率较低。镇痛药常用于治疗肝癌常见的疼痛。肝癌中镇痛靶点 (AT) 的表达变化及其临床意义尚未得到深入了解。
本研究旨在阐明肝癌中 AT 基因的表达模式及其临床意义。通过对转录组数据和临床参数的综合分析,建立与 AT 基因相关的预后模型,并挖掘对 AT 敏感的药物信息。
本研究主要利用来自癌症基因组图谱 (TCGA) 数据库的肝癌患者的转录组数据和临床信息进行分析。这些数据用于分析 AT 的表达、进行生存分析、基因集变异分析 (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合会 (ICGC) 的肝癌患者数据来验证模型的准确性。进一步使用比较毒理学基因组数据库 (CTD) 的数据评估镇痛药对预后模型中关键基因的影响。
该研究调查了 58 种 AT 基因在肝癌与正常组织中的差异表达。根据 AT 表达对患者进行分层,揭示了不同的生存结果。功能富集分析突出了纺锤体组织、中心体和纺锤体微管功能的差异。预后建模确定低表达 TP53 为保护性因素,而高表达 CCNA2、NEU1 和 HTR2C 则为风险因素。常用的镇痛药,包括对乙酰氨基酚和其他药物,被发现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新的思路,并深入了解了其进展的分子机制。
与 AT 相关的基因特征的综合分析表明,它们可能成为肝癌患者的预后预测因子。这些发现不仅为癌症治疗提供了新的思路,也为镇痛药的新适应症开发提供了新的途径。