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:Identifying prognostic biomarkers in oral squamous cell carcinoma: an integrated single-cell and bulk RNA sequencing study on mitophagy-related genes.
Identifying prognostic biomarkers in oral squamous cell carcinoma: an integrated single-cell and bulk RNA sequencing study on mitophagy-related genes.
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口腔鳞状细胞癌(OSCC)的预后极差。近期研究表明,线粒体自噬相关基因(MRGs)与癌症的发生发展密切相关,但其在口腔癌中的作用尚未得到阐明。
我们综合分析了从基因表达综合数据库(GEO)数据集和癌症基因组图谱(TCGA)数据库中获取的单细胞和批量RNA测序(RNA-seq)数据。结合多种方法全面了解OSCC的基因表达模式和生物学特征,如拟时序序列分析、CellChat细胞通讯分析、免疫浸润分析、基因本体论(GO)、LASSO Cox回归、基因集变异分析(GSVA)、京都基因与基因组百科全书(KEGG)、基因集富集分析(GSEA)、肿瘤突变负荷(TMB)及药物敏感性评估。
本研究结果表明,MRGs在OSCC的NK细胞中的活性显著高于其他细胞。利用12个与线粒体自噬强相关的候选基因构建了一个可靠的预后模型。T分期、N分期和风险评分被揭示为独立预后因素。在不同风险组中观察到了特异性富集的通路和免疫细胞。
值得注意的是,低风险患者对化疗更为敏感。此外,通过结合风险评分和临床特征,建立了一个具有优异预测能力的列线图模型。MRGs的活性提示了开发新型靶向治疗的潜力。稳健预后模型的构建也为OSCC患者的个体化预测和临床决策提供了参考价值。
Oral squamous cell carcinoma (OSCC) has an extremely poor prognosis. Recent studies have suggested that mitophagy-related genes (MRGs) are closely correlated with the development and occurrence of cancer, but the role they play in oral cancer has not yet been explained.
We conducted a comprehensive analysis of integrated single-cell and bulk RNA sequencing (RNA-seq) data retrieved from Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) database. Multiple methods were combined to provide a comprehensive understanding of the genetic expression patterns and biology of OSCC, such as analysis of pseudotime series, CellChat cell communication, immune infiltration, Gene Ontology (GO), LASSO Cox regression, gene set variation analysis (GSVA), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), Tumor Mutation Burden (TMB) and drug sensitivity assessments.
The findings of this study demonstrated significantly greater activity of MRGs in NK cells than in other cells in OSCC. A reliable prognostic model was developed using 12 candidate genes strongly associated with mitochondrial autophagy. T stage, N stage and risk score were revealed as independent prognostic factors. Distinctively enriched pathways and immune cells were observed in different risk groups.
Notably, low-risk patients were more responsive to chemotherapy.
In addition, a nomogram model with excellent predictive ability was established by combining the risk scores and clinical features. The activity of MRGs suggest the potential for the development of new targeted therapies. The construction of a robust prognostic model also provides reference value for individualized prediction and clinical decision-making in patients with OSCC.
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