关键词: Gradient boosting model Hepatocellular carcinoma Minimum redundancy maximum relevance Pathomics Prognostic factor Recursive feature elimination TNFRSF4

来  源:   DOI:10.1016/j.heliyon.2024.e31882   PDF(Pubmed)

Abstract:
UNASSIGNED: TNFRSF4 plays a significant role in cancer progression, especially in hepatocellular carcinoma (HCC). This study aims to investigate the prognostic value of TNFRSF4 expression in patients with HCC and to develop a predictive pathomics model for its expression.
UNASSIGNED: A cohort of patients with HCC retrieved from the TCGA database was analyzed using RNA-seq analysis to determine TNFRSF4 expression and its impact on overall survival (OS). Additionally, hematoxylin-eosin staining analysis was performed to construct a pathomics model for predicting TNFRSF4 expression. Then, pathway enrichment analysis was conducted, immune checkpoint markers were investigated, and immune cell infiltration was examined to explore the underlying biological mechanism of the pathomics score.
UNASSIGNED: TNFRSF4 expression was significantly higher in tumor tissues than in normal tissues. TNFRSF4 expression also exhibited significant correlations with various clinical variables, including pathologic stage III/IV and R1/R2/RX residual tumor. Furthermore, elevated TNFRSF4 expression was associated with unfavorable OS. Interestingly, in the subgroup analysis, elevated TNFRSF4 expression was identified as a significant risk factor for OS in male patients. The newly developed pathomics model successfully predicted TNFRSF4 expression with good performance and revealed a significant association between high pathomics scores and worse OS. In male patients, high pathomics scores were also associated with a higher risk of mortality. Moreover, pathomics scores were also involved in specific hallmarks, immune-related characteristics, and apoptosis-related genes in HCC, such as epithelial-mesenchymal transition, Tregs, and BAX expression.
UNASSIGNED: Our findings suggest that TNFRSF4 expression and the newly devised pathomics scores hold potential as prognostic markers for OS in patients with HCC. Additionally, gender influenced the association between these markers and patient outcomes.
摘要:
TNFRSF4在癌症进展中起重要作用,尤其是肝细胞癌(HCC)。本研究旨在探讨TNFRSF4表达在HCC患者中的预后价值,并建立其表达的预测病理组学模型。
使用RNA-seq分析对从TCGA数据库检索的一组HCC患者进行分析,以确定TNFRSF4表达及其对总生存期(OS)的影响。此外,进行苏木精-伊红染色分析以构建用于预测TNFRSF4表达的病理组学模型。然后,进行了途径富集分析,免疫检查点标记进行了调查,和免疫细胞浸润检查,以探索病理组学评分的潜在生物学机制。
TNFRSF4在肿瘤组织中的表达明显高于正常组织。TNFRSF4表达也表现出与各种临床变量的显著相关性,包括病理分期III/IV和R1/R2/RX残留肿瘤。此外,升高的TNFRSF4表达与不良OS相关.有趣的是,在亚组分析中,在男性患者中,升高的TNFRSF4表达被认为是OS的重要危险因素.新开发的病理组学模型以良好的性能成功地预测了TNFRSF4的表达,并揭示了高病理组学得分与较差OS之间的显着关联。在男性患者中,较高的病理组学评分也与较高的死亡风险相关.此外,病理组学评分也涉及特定的标志,免疫相关特征,和凋亡相关基因在肝癌,如上皮-间质转化,Tregs,和BAX表达式。
我们的研究结果表明,TNFRSF4表达和新设计的病理组学评分在HCC患者中具有作为OS预后标志物的潜力。此外,性别影响这些标志物与患者结局之间的关联.
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