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:A comprehensive analysis to reveal the underlying molecular mechanisms of natural killer cell in thyroid carcinoma based on single-cell RNA sequencing data.
A comprehensive analysis to reveal the underlying molecular mechanisms of natural killer cell in thyroid carcinoma based on single-cell RNA sequencing data.
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重要信号通路、分子和药物的识别为 THCA 的进一步研究提供了潜在的研究方向,并有助于该疾病诊断和治疗方法的开发。
甲状腺癌(THCA)是内分泌系统最常见的癌症。自然杀伤(NK)细胞在肿瘤免疫监视中发挥重要作用。本研究旨在探索NK细胞在THCA中可能涉及的分子机制,以帮助该疾病的管理和治疗。
所有数据均从公共数据库下载。通过limma、WGCNA和singleR包鉴定与THCA中NK细胞相关的候选hub基因。对候选hub基因进行功能富集分析。通过Pearson相关分析鉴定与NK细胞相关的hub基因。构建mRNA-miRNA-lncRNA和转录因子(TF)网络并预测药物。
NK 细胞在 THCA 组织中的浸润水平高于癌旁组织。KEGG 功能富集分析仅获得两条信号通路,即甲状腺激素合成和矿物质吸收。通过 Pearson 相关性分析鉴定出的 CTSC、FN1、SLC34A2 和 TMSB4X 被认为是枢纽基因。受试者工作特征分析提示,枢纽基因可能是潜在的诊断生物标志物。在 mRNA-miRNA-lncRNA 网络中,FN1 与 IQCH-AS1 的相关性最高,IQCH-AS1 也与 hsa-miR-543 相关。此外,在 TF 网络中还发现 FN1 与 RUNX1 的相关性最高。最后,基于 ASGARD 鉴定出 NK 细胞相关药物 belinostat 和 vorinostat。
Thyroid carcinoma (THCA) is the most common cancer of the endocrine system. Natural killer (NK) cell play an important role in tumor immune surveillance. The aim of this study was to explore the possible molecular mechanisms involved in NK cell in THCA to help the management and treatment of the disease.
All data were downloaded from public databases. Candidate hub genes associated with NK cell in THCA were identified by limma, WGCNA and singleR packages. Functional enrichment analysis was performed on the candidate hub genes. Hub genes associated with NK cell were identified by Pearson correlation analysis. The mRNA-miRNA-lncRNA and transcription factors (TF) networks were constructed and the drug was predicted.
The infiltration level of NK cell in THCA tissues was higher than that in paracancerous tissues. KEGG functional enrichment analysis only obtained two signaling pathways, thyroid hormone synthesis and mineral absorption. CTSC, FN1, SLC34A2 and TMSB4X identified by Pearson correlation analysis were considered as the hub genes. Receiver operating characteristic analysis suggested that hub genes may be potential diagnostic biomarkers. In mRNA-miRNA-lncRNA network, FN1 had the highest correlation with IQCH-AS1, and IQCH-AS1 was also correlated with hsa-miR-543. In addition, FN1 and RUNX1 were also found to have the highest correlation in TF network. Finally, NK cell-related drugs belinostat and vorinostat were identified based on ASGARD.
The identification of important signaling pathways, molecules and drugs provides potential research directions for further research in THCA and contributes to the development of diagnostic and therapeutic approaches for this disease.
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