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:Comprehensive prognostic and immune analysis of sterol O-acyltransferase 1 in patients with hepatocellular carcinoma.
Comprehensive prognostic and immune analysis of sterol O-acyltransferase 1 in patients with hepatocellular carcinoma.
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我们的发现表明,SOAT1 可能作为 HCC 治疗的新靶点,有助于开发免疫治疗和代谢治疗的新策略。
甾醇O-酰基转移酶1(SOAT1)是肝癌诊断和治疗的重要靶点。然而,SOAT1在肝细胞癌(HCC)患者中的预后价值仍不明确。
探讨SOAT1表达与HCC的相关性,利用癌症基因组图谱(TCGA)-肝细胞癌(LIHC)及泛癌的RNA-seq和基因表达数据。
分析SOAT1表达与HCC之间的相关性。采用Cox风险回归模型探讨SOAT1在HCC中的预后价值。基于TCGA-LIHC数据探讨总生存期和疾病特异性生存期。通过对差异表达基因进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)分析,表征由SOAT1介导的生物学过程和功能通路。此外,还进行了SOAT1在HCC中的蛋白质-蛋白质相互作用网络和共表达分析,以更好地理解SOAT1在该恶性肿瘤中的调控机制。
SOAT1和SOAT2在非配对样本中高表达,而仅在配对样本中SOAT1高表达。SOAT1表达在LIHC患者肿瘤样本与癌旁组织比较中的受试者工作特征曲线下面积为0.748,而SOAT1表达在LIHC患者肿瘤样本与GTEx比较中的曲线下面积为0.676。SOAT1表达较高的患者生存率较低。GO/KEGG和基因集富集分析的结果表明,PI3K/AKT信号通路、IL-18信号通路、钙信号通路、分泌因子、Wnt信号通路、Jak/STAT信号通路、MAPK家族信号通路以及细胞间通讯参与了这种关联。SOAT1表达与巨噬细胞、Th2细胞、辅助性T细胞、CD56 brightNK 细胞和Th1细胞的丰度呈正相关,与Th17细胞、树突状细胞和细胞毒性细胞的丰度呈负相关。
Sterol O-acyltransferase 1 (SOAT1) is an important target in the diagnosis and treatment of liver cancer. However, the prognostic value of SOAT1 in patients with hepatocellular carcinoma (HCC) is still not clear. AIM: To investigate the correlation of SOAT1 expression with HCC, using RNA-seq and gene expression data of The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) and pan-cancer.
The correlation between SOAT1 expression and HCC was analyzed. Cox hazard regression models were conducted to investigate the prognostic value of SOAT1 in HCC. Overall survival and disease-specific survival were explored based on TCGA-LIHC data. Biological processes and functional pathways mediated by SOAT1 were characterized by gene ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes. In addition, the protein-protein interaction network and co-expression analyses of SOAT1 in HCC were performed to better understand the regulatory mechanisms of SOAT1 in this malignancy.
SOAT1 and SOAT2 were highly expressed in unpaired samples, while only SOAT1 was highly expressed in paired samples. The area under the receiver operating characteristic curve of SOAT1 expression in tumor samples from LIHC patients compared with para-carcinoma tissues was 0.748, while the area under the curve of SOAT1 expression in tumor samples from LIHC patients compared with GTEx was 0.676. Patients with higher SOAT1 expression had lower survival rates. Results from GO/KEGG and gene set enrichment analyses suggested that the PI3K/AKT signaling pathway, the IL-18 signaling pathway, the calcium signaling pathway, secreted factors, the Wnt signaling pathway, the Jak/STAT signaling pathway, the MAPK family signaling pathway, and cell-cell communication were involved in such association. SOAT1 expression was positively associated with the abundance of macrophages, Th2 cells, T helper cells, CD56 bright natural killer cells, and Th1 cells, and negatively linked to the abundance of Th17 cells, dendritic cells, and cytotoxic cells.
Our findings demonstrate that SOAT1 may serve as a novel target for HCC treatment, which is helpful for the development of new strategies for immunotherapy and metabolic therapy.
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