PDF(Pubmed)
Abstract：
Neutrophil extracellular traps (NETs) and other factors play a significant role in impacting the prognosis of patients with Hepatocellular carcinoma (HCC). Nevertheless, further research is warranted to fully elucidate the prognostic implications of NETs in patients with HCC. We employed a hierarchical clustering technique to examine the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) data and identified subtypes associated with NETs. Subsequently, we utilized LASSO regression analysis to identify a distinct gene expression pattern within these subtypes. The strength of this signature was further validated through analysis of TCGA-LIHC and International Cancer Genome Consortium-Liver Cancer (ICGC-LIRI-JP) data. Our findings resulted in the construction of a six-gene signature related to NETs, which can predict survival outcomes in HCC patients. To enhance the predictive accuracy of our tool, we developed a nomogram that integrates the NETs signature with clinicopathological characteristics. We validated the significance of NETs in HCC patients using qRT-PCR and immunohistochemistry assays, along with in vitro experiments targeting high-risk genes. Furthermore, our exploration of the immune microenvironment uncovered augmented immune-specific metrics within the low-risk cohort, implying potential disparities in immune-related attributes between the high-risk and low-risk contingents. In summary, the NETs signature we discovered serves as a valuable biomarker and provides guidance for personalized therapy in HCC patients.
摘要：
中性粒细胞胞外诱捕网(NETs)等因素对肝细胞癌(HCC)患者的预后有重要影响。然而，需要进一步的研究来充分阐明NETs对HCC患者预后的影响.我们采用分层聚类技术来检查癌症基因组图谱-肝细胞癌（TCGA-LIHC）数据并确定与NET相关的亚型。随后，我们利用LASSO回归分析来鉴定这些亚型中不同的基因表达模式.通过分析TCGA-LIHC和国际癌症基因组联盟-肝癌(ICGC-LIRI-JP)数据进一步验证了该签名的强度。我们的发现导致构建了与NET相关的六基因签名，这可以预测肝癌患者的生存结果。为了提高我们工具的预测准确性，我们建立了一个列线图,将NETs信号与临床病理特征结合起来.我们使用qRT-PCR和免疫组织化学测定法验证了NETs在HCC患者中的意义，以及针对高风险基因的体外实验。此外，我们对免疫微环境的探索发现了低风险队列中增强的免疫特异性指标，这意味着高风险和低风险突发事件之间免疫相关属性的潜在差异。总之,我们发现的NETs特征可作为一种有价值的生物标志物,为HCC患者的个性化治疗提供指导.
