Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Neurology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
J Gene Med. 2023 Nov;25(11):e3551. doi: 10.1002/jgm.3551. Epub 2023 Jul 3.
Hepatocellular carcinoma (HCC) is a malignant disease with a high incidence rate, high mortality and poor prognosis. Neutrophil extracellular traps (NETs), as an extracellular reticular structure, promote the development and progression of cancer in the tumor microenvironment, and have a promising prospect as a prognostic indicator. In the present study, we elucidated the prognostic value of NET-related genes.
The NETs gene pair of The Cancer Genome Atlas cohort was constructed by least absolute shrinkage and selection operator analysis. Samples from the International Cancer Genome Consortium were performed to verify its feasibility. Kaplan-Meier analysis was used to compare the overall survival (OS) rate of the two subgroups. The independent predictors of OS were determined by univariate and multivariate Cox analysis. Furthermore, Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were analyzed by gene set enrichment analysis. The single sample gene set enrichment analysis method was performed to deplore the relationship of risk score with tumor immune microenvironment. The GSE149614 dataset was applied as single cell RNA level validation. PCR was performed to the detect mRNA expression profiles of NETs-related genes.
Our analysis of the NETs-related model provides a promising prospect as a prognostic indicator. The OS of high-risk group patients was significantly reduced. The risk score was an important independent predictor of HCC prognosis. The Nomogram model suggested a favorable classification performance. The drug resistance and sensitivity of tumor cells to chemotherapeutics was significantly correlated with the prognostic gene expression. The immune status of the two risk groups showed a marked difference.
The novel prognostic gene pair and immune landscape could predict the prognosis of HCC patients and provide a new understanding of immunotherapy in HCC.
肝细胞癌（HCC）是一种发病率高、死亡率高、预后差的恶性疾病。中性粒细胞胞外诱捕网（NETs）作为细胞外的网状结构，在肿瘤微环境中促进癌症的发展和进展，作为一种预后指标具有广阔的前景。本研究阐明了与 NET 相关的基因的预后价值。
通过最小绝对收缩和选择算子分析构建了癌症基因组图谱队列的 NETs 基因对。对国际癌症基因组联合会的样本进行验证，以验证其可行性。采用 Kaplan-Meier 分析比较两组的总生存率（OS）。采用单因素和多因素 Cox 分析确定 OS 的独立预测因子。此外，通过基因集富集分析对基因进行功能分析。采用单样本基因集富集分析方法探讨风险评分与肿瘤免疫微环境的关系。应用 GSE149614 数据集进行单细胞 RNA 水平验证。采用 PCR 检测 NETs 相关基因的 mRNA 表达谱。
NETs 相关模型的分析为预后指标提供了有前景的预测。高危组患者的 OS 明显降低。风险评分是 HCC 预后的重要独立预测因子。列线图模型提示具有良好的分类性能。肿瘤细胞对化疗药物的耐药性和敏感性与预后基因表达显著相关。两组的免疫状态存在明显差异。
新型预后基因对和免疫图谱可以预测 HCC 患者的预后，并为 HCC 的免疫治疗提供新的认识。
