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 and validation of Rab GTPases RAB13 as biomarkers for peritoneal metastasis and immune cell infiltration in colorectal cancer patients.
Identification and validation of Rab GTPases RAB13 as biomarkers for peritoneal metastasis and immune cell infiltration in colorectal cancer patients.
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我们的研究表明 RAB13 在 CRC-PM 中具有临床作用,提示其未来可能作为治疗靶点。
作为最常见的癌症之一,结直肠癌(CRC)具有高发病率和死亡率。腹膜转移(PM)是CRC的致命状态,很少有患者能从传统治疗中获益。PM与免疫细胞浸润之间存在复杂的相互作用。因此,我们旨在确定与结直肠癌腹膜转移(CRCPM)相关的生物标志物及其与免疫细胞浸润的关系。
通过信息学分析,筛选出差异表达基因(DEGs)并筛选出核心基因。RAB13作为核心基因之一,从公共数据库中鉴定并在CRC组织中得到验证。应用ESTIMATE、CEBERSORT和TIMER算法分析RAB13与CRC免疫浸润的相关性。在scRNA-Seq中,在单细胞水平上分析RAB13在不同细胞中的表达。对RAB13进行基因集富集分析(GSEA)并进一步确认。使用oncoPredict算法评估RAB13对药物敏感性的影响。
在公共数据库中发现RAB13高表达,并导致不良预后。发现RAB13与巨噬细胞及其他免疫细胞浸润呈正相关,通过scRNA-Seq发现RAB13定位于CRC细胞和巨噬细胞中。GSEA揭示高RAB13表达富集于多种生物信号通路,oncoPredict算法显示RAB13表达与紫杉醇敏感性相关。
As one of the most common cancer, colorectal cancer (CRC) is with high morbidity and mortality. Peritoneal metastasis (PM) is a fatal state of CRC, and few patients may benefit from traditional therapies. There is a complex interaction between PM and immune cell infiltration. Therefore, we aimed to determine biomarkers associated with colorectal cancer peritoneal metastasis (CRCPM) and their relationship with immune cell infiltration.
By informatic analysis, differently expressed genes (DEGs) were selected and hub genes were screened out. RAB13, one of the hub genes, was identificated from public databases and validated in CRC tissues. The ESTIMATE, CEBERSORT and TIMER algorithms were applied to analyze the correlation between RAB13 and immune infiltration in CRC. RAB13's expression in different cells were analyzed at the single-cell level in scRNA-Seq. The Gene Set Enrichment Analysis (GSEA) was performed for RAB13 enrichment and further confirmed. Using oncoPredict algorithm, RAB13's impact on drug sensitivity was evaluated.
High RAB13 expression was identified in public databases and led to a poor prognosis. RAB13 was found to be positively correlated with the macrophages and other immune cells infiltration and from scRNA-Seq, RAB13 was found to be located in CRC cells and macrophages. GSEA revealed that high RAB13 expression enriched in a various of biological signaling, and oncoPredict algorithm showed that RAB13 expression was correlated with paclitaxel sensitivity.
Our study indicated clinical role of RAB13 in CRC-PM, suggesting its potential as a therapeutic target in the future.
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