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:NK cell-associated LncRNA signature predicts prognosis and immune landscape in hepatocellular carcinoma.
NK cell-associated LncRNA signature predicts prognosis and immune landscape in hepatocellular carcinoma.
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本研究旨在建立并验证基于自然杀伤(NK)细胞相关长链非编码RNA(lncRNA)的风险模型,以预测肝细胞癌(HCC)患者结局。为进一步探讨NK细胞在HCC肿瘤微环境中的作用,我们利用单细胞RNA测序数据和TCGA-LIHC数据集鉴定NK细胞相关lncRNA。通过Cox回归和LASSO方法,确定了模型中作为预后标志物的4种关键lncRNA。该模型在训练集、验证集及整体数据集中均表现出稳健的预测能力。此外,我们发现NK细胞与其他免疫细胞,尤其是CD8+ T细胞之间存在协同作用。我们还发现了新的HCC分子亚群及其与免疫微环境和药物敏感性的关联。为进一步验证这些发现,我们对模型lncRNA的表达和功能进行了实验验证。结果提示,NK细胞相关lncRNA模型不仅可作为预测HCC患者结局的有效预后工具,还可能提供免疫治疗和靶向治疗的分子靶点。
The purpose of this investigation was to develop and validate a risk model based on natural killer (NK) cell-associated lncRNAs to predict outcomes in individuals with hepatocellular carcinoma (HCC). To further explore the role of NK cells in the HCC tumor microenvironment, we leveraged single-cell RNA sequencing data and the TCGA-LIHC dataset to identify NK cell-associated lncRNAs.
Using Cox regression and LASSO techniques, we pinpointed four key lncRNAs as prognostic markers for the model. The model demonstrated robust predictive power across the training set, validation set, and entire dataset.
Additionally, we identified a synergistic interaction between NK cells and other immune cells, particularly CD8 + T cells, in HCC.
Moreover, we uncovered novel molecular subgroups of HCC and their associations with the immune microenvironment and drug sensitivity. To further validate these findings, we performed experimental validation of the expression and function of the model lncRNAs in HCC. These results suggest that the NK cell-associated lncRNA model not only serves as an effective prognostic tool for HCC patient outcomes but also offers potential molecular targets for immunotherapy and targeted therapies.
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