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:LRRC25 Is a Potential Biomarker for Predicting Immunotherapy Response in Patients with Gastric Cancer.
LRRC25 Is a Potential Biomarker for Predicting Immunotherapy Response in Patients with Gastric Cancer.
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高 LRRC25 表达通过影响胃癌中的趋化因子轴促进免疫抑制微环境。LRRC25 可能作为临床上预测胃癌患者新辅助免疫治疗反应的有用生物标志物。LRRC25 可影响 NK 细胞的表型和功能。
富含亮氨酸重复序列25(LRRC25)在不同肿瘤类型中具有差异性表达,但其与胃癌免疫细胞浸润的关系仍不清楚。我们利用癌症基因组图谱的泛癌数据和基因表达综合数据库的基因数据分析了LRRC25的表达。进一步使用来自临床试验(编号NCT04208347)的胃癌组织评估其临床意义。
通过对TCGA数据库和UCSC Xena数据库的生物信息学分析,我们发现了LRRC15、胃癌与免疫细胞浸润之间的相关性。进一步,多重免疫组织化学/免疫荧光(mIHC/IF)、组织芯片以及图像采集和定量分析证实了我们的理论。
研究发现LRRC25在胃癌中高表达。进一步分析显示,LRRC25的表达与免疫相关基因集有关,包括固有免疫、适应性免疫和趋化因子信号通路中的基因集。mIHC/IF的结果提示LRRC25与抗PD-1治疗反应呈负相关,并揭示LRRC25+细胞与CD16表达呈一致变化的趋势。我们还发现LRRC25表达与免疫细胞浸润水平显著相关。特别是,LRRC25与NK细胞的表型和功能之间存在关系。
Leucine-rich repeat containing 25 (LRRC25) is distinguishingly expressed in different tumor types, but the relationship with immune cell infiltration in gastric cancer stills unclear. We analyzed LRRC25 expression using pan-cancer data from The Cancer Genome Atlas and gene data from Gene Expression Omnibus. The clinical significance was further evaluated using gastric cancer tissues derived from clinical trials (no. NCT04208347). METHOD: Through bioinformatics analysis of TCGA database and the UCSC Xena database, we found the correlation between LRRC15, gastric cancer, and immune cell infiltration. Further, multiplex immunohistochemistry/immunofluorescence (mIHC/IF), tissue microarray, and image acquisition and quantitative analysis confirmed our theory.
It was discovered that LRRC25 was highly expressed in gastric cancer. Further analysis revealed that the expression of LRRC25 associated with gene sets implicated in immunity, including those in innate immunity, adaptive immunity, and chemokine signaling pathways. The result of (mIHC/IF) suggests a negative relevance between LRRC25 and response of anti-PD-1 treatment and reveals a trend of consistent change on LRRC25 + cells and CD16 expression. We also discovered that LRRC25 expression significantly associated with immune cell infiltration level. In particular, there is a relationship between LRRC25 and the phenotype and function of NK cells.
High LRRC25 expression contributes to immunosuppressive microenvironment by influencing chemokine axis in gastric cancer. LRRC25 may serve as a clinically useful biomarker for predicting neoadjuvant immunotherapeutic response in patients with gastric cancer. LRRC25 can affect the phenotype and function of NK cells.
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