RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Identification of TXNIP, FTCD, and HAGH as Key Genes in a Cancer Stem Cell-driven Prognostic Model for Hepatocellular Carcinoma.
Identification of TXNIP, FTCD, and HAGH as Key Genes in a Cancer Stem Cell-driven Prognostic Model for Hepatocellular Carcinoma.
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本研究确定了与 HCC 预后、TME 和药物反应相关的 CSC 相关模块,为模型的临床应用提供了潜在的机制基础。识别出了潜在的预后和靶向治疗生物标志物。基于 CSC 相关模块的预后模型可能为 HCC 的个性化治疗提供新工具。
本研究基于高维WGCNA(hdWGCNA)识别的癌症干细胞(CSC)相关模块,开发了肝细胞癌(HCC)的预后模型。
对scRNA-seq数据进行过滤、降维和聚类以用于下游分析。通过hdWGCNA鉴定CSC相关模块。基于TCGA肝细胞癌(LIHC)数据,我们利用单因素Cox、LASSO和逐步回归分析构建了预后RiskScore模型,并在ICGC-LIRI-JP数据集中进行了验证。分析了该模型与肿瘤免疫微环境(TME)及药物敏感性之间的相关性。
鉴定出9个细胞亚群,其中包括CSCs,这些亚群在肿瘤中显著富集。hdWGCNA鉴定出6个与CSC相关的关键模块。基于TXNIP、FTCD和HAGH构建的预后RiskScore模型在两个队列中均表现出AUC > 0.6。高RiskScore与免疫抑制性TME相关,其特征为中性粒细胞、NK细胞和嗜酸性粒细胞下调,以及对Pyrimethamine和Vinorelbine等化疗药物更高的敏感性。
The scRNA-seq data were filtered, dimensionally reduced, and clustered for downstream analysis. CSC-related modules were identified by hdWGCNA. Based on the TCGA liver hepatocellular carcinoma (LIHC) data, we developed a prognostic RiskScore model using univariate Cox, LASSO, and stepwise regression analyses and validated in the ICGC-LIRI-JP dataset. Correlations between the model and the tumor immune microenvironment (TME) and drug sensitivity were analyzed.
Nine cell subpopulations, including CSCs, were identified and were significantly enriched in tumors. hdWGCNA identified six CSC-related key modules. The prognostic RiskScore model, developed based on TXNIP, FTCD, and HAGH, exhibited an AUC > 0.6 in both cohorts. A high RiskScore was correlated with an immunosuppressive TME characterized by downregulated neutrophils, NK cells, and eosinophils, and higher sensitivity to chemotherapeutic agents such as Pyrimethamine and Vinorelbine. DISCUSSION: This study identified CSC-related modules associated with HCC prognosis, TME, and drug response, providing a potential mechanistic basis for the clinical application of the model.
Potential prognostic and targeted therapy biomarkers were identified. The CSC-related module-based prognostic model may offer a new tool for personalized HCC treatment.
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