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 diagnostic biomarkers and immune cell infiltration in tongue squamous cell carcinoma using bioinformatic approaches.
Identification of diagnostic biomarkers and immune cell infiltration in tongue squamous cell carcinoma using bioinformatic approaches.
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我们的发现表明,SPP1 可作为 TSCC 的诊断生物标志物,并参与 TSCC 组织内的免疫细胞浸润。SPP1 与巨噬细胞之间的相关性可能为 TSCC 的靶向治疗研究提供新的见解。
本研究采用生物信息学方法识别舌鳞状细胞癌(TSCC)的诊断生物标志物,并探讨TSCC中免疫细胞的浸润情况,以及生物标志物与免疫细胞之间的关系。
我们从数据库获取了TSCC表达数据集,并使用R软件对TSCC与邻近正常组织进行了差异基因表达分析。利用DAVID网站对差异表达基因(DEGs)进行了富集分析。构建了DEGs的蛋白质相互作用网络,并使用STRING和Cytoscape等工具识别了枢纽基因。进行了生存分析以识别诊断生物标志物,并使用Cibersort软件的逆卷积算法分析了TSCC中免疫细胞的浸润。最后,通过临床病理切片验证了所发现分子的表达。
我们在TSCC中鉴定出24个DEGs,主要与信号转导、物质代谢、先天免疫应答及其他相关信号通路有关。通过构建蛋白质-蛋白质相互作用(PPI)网络筛选出的24个枢纽基因中,有7个(MMP13、POSTN、MMP9、MMP10、MMP3、SPP1、MMP1)具有预后价值。生存分析表明,SPP1具有诊断潜力。SPP1基因的表达水平与TSCC以及多种免疫细胞类型相关,包括巨噬细胞M0、M1、M2、CD8 + T细胞、活化NK细胞和单核细胞(p < 0.05)。组织学结果证实,与癌旁非癌组织相比,SPP1在TSCC组织中表达更高,尤其是在表达CD68的巨噬细胞中。
In this study, we employed a bioinformatics approach to identify diagnostic biomarkers for tongue squamous cell carcinoma (TSCC) and investigate the infiltration of immune cells in TSCC, as well as the relationship between biomarkers and immune cells.
We obtained the TSCC expression dataset from a database and conducted differential gene expression analysis between TSCC and adjacent normal tissues using R software. Enrichment analysis of the differentially expressed genes (DEGs) was performed using the DAVID website. Protein interaction networks for the DEGs were constructed, and hub genes were identified using tools such as STRING and Cytoscape. Survival analysis was conducted to identify diagnostic biomarkers and the infiltration of immune cells in TSCC was analyzed using the inverse convolution algorithm with Cibersort software. Finally, the expression of the discovered molecules was verified through clinical pathological sections.
We identified 24 DEGs in TSCC, primarily associated with signal transduction, substance metabolism, innate immune response, and other related signaling pathways. Among the 24 hub genes screened through the construction of a protein-protein interaction (PPI) network, seven (MMP13, POSTN, MMP9, MMP10, MMP3, SPP1, MMP1) exhibited prognostic value. Survival analysis indicated that SPP1 demonstrated diagnostic potential. The expression level of the SPP1 gene showed a correlation with TSCC as well as several immune cell types, including macrophage M0, M1, M2, CD8 + T cell, activated NK cell, and monocyte (p < 0.05). Histological results confirmed higher expression of SPP1 in TSCC tissues compared to adjacent non-cancerous tissues, particularly in CD68-expressing macrophages.
Our findings suggest that SPP1 serves as a diagnostic biomarker for TSCC and is involved in immune cell infiltration within TSCC tissues. The correlation between SPP1 and macrophages may offer new insights for targeted therapeutic research on TSCC.
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