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:Stemness-related gene signature for predicting therapeutic response in patients with esophageal cancer.
Stemness-related gene signature for predicting therapeutic response in patients with esophageal cancer.
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NCAPG [log 2 fold change (FC) =1.81; q value =2.68×10 -11 ] 在 ESCA 中显著上调,并与静息自然杀伤 (NK) 细胞呈正相关,提示人 NK 细胞通过 ESCA 中 NCAPG 的过表达而处于静息状态。hsa-miR-1269a 在具有不良预后特征的 ESCA 患者中显著上调。CD4 + 静息记忆 T 细胞 (P<0.01) 与 hsa-miR-1269a 呈显著负相关。本研究提出的见解将有助于开发用于治疗 ESCA 患者的创新疗法。
大量研究表明,肿瘤干性促进肿瘤进展。然而,干性相关基因(SRGs)在食管癌(ESCA)中的潜在作用仍不清楚。
本研究鉴定了ESCA中差异表达的干性相关(DESR)信使RNA(mRNA)、微小RNA(miRNA)和长链非编码RNA(lncRNA),并将其与ESCA患者的临床特征相关联,以构建预后风险评估模型。通过功能分析、蛋白质-蛋白质相互作用(PPI)分析、竞争性内源RNA(ceRNA)网络以及肿瘤浸润免疫细胞分析来验证模型所得结果。
对干性富集评分进行相关性分析,从癌症基因组图谱食管癌(TCGA-ESCA)数据集中鉴定出1,106个DESR基因(DESRGs)、84个DESRmiRNAs和320个DESRlncRNAs。进行网络聚类并鉴定出前20个连接点,包括连接136个相邻节点的CDC20。构建了一个ceRNA网络,包括17个DESRmiRNAs、44个DESRlncRNAs和55个DESRGs。
Extensive research has indicated that tumor stemness promotes tumor progression. However, the underlying role of stemness-related genes (SRGs) in esophageal cancer (ESCA) remains unclear.
This study identified differentially expressed stemness-related (DESR) messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) in ESCA, and correlated them with the clinical features of patients with ESCA to develop a prognostic risk assessment model. Functional analysis, protein-protein interaction (PPI) analysis, competing endogenous RNA (ceRNA) networks, and tumor-infiltrating immune cell analyses were performed to corroborate the results obtained from the model.
Correlation analysis of the stemness enrichment scores revealed 1,106 DESR genes (DESRGs), 84 DESRmiRNAs, and 320 DESRlncRNAs were identified from The Cancer Genome Atlas Esophageal Carcinoma (TCGA-ESCA) dataset. Network clustering was performed and the top 20 connection points were identified, including CDC20 that connects to 136 adjacent nodes. A ceRNA network was constructed, including 17 DESRmiRNAs, 44 DESRlncRNAs, and 55 DESRGs.
NCAPG [log 2 fold change (FC) =1.81; q value =2.68×10 -11 ] was significantly upregulated in ESCA and positively correlated with resting natural killer (NK) cells, suggesting that human NK cells rest via the overexpression of NCAPG in ESCA. hsa-miR-1269a is significantly upregulated in ESCA patients with poor prognostic features. CD4 + resting memory T cells (P<0.01) were significantly negatively correlated with hsa-miR-1269a . The insights presented in this study will contribute to the development of innovative therapeutics for the treatment of patients with ESCA.
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