为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Prognostic Significance of Iron Metabolism and Immune-Related Genes as Risk Markers in Hepatocellular Carcinoma.
Prognostic Significance of Iron Metabolism and Immune-Related Genes as Risk Markers in Hepatocellular Carcinoma.
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肝细胞癌(HCC)是一种高度致命的肝癌,具有显著的异质性,这给预后和治疗结果的预测带来了挑战。铁代谢和免疫相关基因(IMRGs)对HCC患者预后的影响仍不清楚。
我们利用癌症基因组图谱(TCGA)数据集获取HCC患者的mRNA表达数据和临床信息。通过应用LASSO回归以及单因素/多因素Cox回归分析,我们识别出五个与HCC患者生存显著相关的IMRGs。
我们构建了一个包含这五个基因的预后模型。该模型表现出优异的预测性能,不仅在TCGA数据集中如此,在使用基因表达综合数据库(GEO)数据集进行验证时也是如此。基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析显示,在顶端质膜和含胶原细胞外基质等功能类别上存在显著差异。包括PI3K-AKT信号通路和钙信号通路在内的若干通路,在不同预后的HCC患者之间表现出显著差异(P < 0.05)。免疫浸润分析表明,高风险组中多种免疫细胞、免疫功能和免疫检查点(如B细胞、CD8+ T细胞和TILs)的水平显著较低(P < 0.05)。免疫表型评分结果提示,低风险组可能对免疫治疗表现出更有利的反应。
此外,CellMiner数据库预测了与预后基因显著相关的抗肿瘤药物(P < 0.001)。总之,我们的研究结果强调了IMRGs在HCC预后和免疫治疗中的预测作用,表明ADAMTS13、CRHBP、VIPR1、FCN3和CLEC1B可能作为HCC潜在的预后生物标志物。
Hepatocellular carcinoma (HCC) is a highly lethal liver cancer with significant heterogeneity, which poses challenges in predicting prognosis and treatment outcomes. The impact of iron metabolism and immune-related genes (IMRGs) on HCC patient prognoses remains elusive.
We utilized The Cancer Genome Atlas (TCGA) dataset to obtain mRNA expression data and clinical information from HCC patients. Through the application of LASSO regression and univariate/multivariate Cox regression analyses, we identified five IMRGs significantly associated with survival of HCC patients.
We constructed a prognostic model comprising these five genes. The model demonstrated excellent predictive performance, not only within TCGA dataset but also when validated using the Gene Expression Omnibus (GEO) dataset. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses presented significant variations in functional categories, such as apical plasma membrane and collagen-containing extracellular matrix.
Several pathways, including the PI3K-AKT signaling pathway and the calcium signaling pathway, exhibited significant variations among HCC patients with varying prognoses (P < 0. 05). Immune infiltration analysis indicated significantly lower levels of various immune cells, immune functions, and immune checkpoints, such as B cells, CD8+ T cells, and TILs, in the high-risk group (P < 0. 05). Immunophenoscore results suggested that the low-risk group may exhibit a more favorable response to immune therapy.
Furthermore, the CellMiner database predicted anti-tumor drugs significantly associated with prognostic genes (P < 0. 001).
In conclusion, our findings highlight the predictive role of IMRGs in prognosis and immune treatment of HCC, indicating that ADAMTS13, CRHBP, VIPR1, FCN3, and CLEC1B may serve as potential prognostic biomarkers for HCC.
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