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 biomarkers related to Tumor-Infiltrating Lymphocytes (TILs) infiltration with gene co-expression network in colorectal cancer.
Identification of biomarkers related to Tumor-Infiltrating Lymphocytes (TILs) infiltration with gene co-expression network in colorectal cancer.
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结直肠癌(CRC)是最常见的肿瘤之一,在全球癌症死因中排名第二。晚期患者的预后仍然很差。本研究基于基因表达综合数据库中的CRC表达数据,通过加权基因共表达网络分析,识别出与肿瘤浸润免疫细胞关联最强的核心模块。随后,通过共表达网络和预后分析,识别出三个与浸润免疫细胞相关的核心基因(ADAM8、IL-1A、VAV3)。经过TIMER数据库的分析和验证,选择ADAM8作为预后生物标志物。最后,功能试验结果表明,ADAM8基因表达下调部分逆转了CRC细胞对TIL的免疫耐受。通过生物信息学分析方法和实验技术,我们确定了ADAM8作为CRC中与肿瘤浸润免疫细胞相关的预后生物标志物和临床治疗靶点。
Colorectal cancer (CRC) is one of the most common tumors, ranking second in the global cause of death from cancer. The prognosis of advanced patients is still very poor. In this study, hub modules with the highest association with tumor-infiltrating immune cells were identified by weighted gene co-expression network analysis based on CRC expression data from the Gene Expression Omnibus database.
Next, three hub genes (ADAM8, IL-1A, VAV3) related to infiltrating immune cells were identified by co-expression network and prognostic analysis. After analysis and verification of the TIMER database, ADAM8 was selected as a prognostic biomarker.
Finally, the result of functional test showed that ADAM8 gene expression down-regulation partially reversed the immune tolerance of CRC cells to TILs. By bioinformatics analysis methods and the experimental techniques, we identified ADAM8 as a prognostic biomarker and clinical therapeutic target related to tumor-infiltrating immune cells in CRC.
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