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:Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy.
Integration of Chemoinformatics and Multi-Omics Analysis Defines ECT2 as a Potential Target for Cancer Drug Therapy.
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上皮细胞转化2(ECT2)是一个潜在的癌基因,近期多项研究已将其与多种人类癌症的进展相关联。尽管肿瘤学相关报道中对ECT2的关注日益增加,但目前尚无综合性研究来汇总和整合ECT2在一组人类癌症中的表达及致癌行为。
本研究首先对ECT2在癌组织与正常组织中的差异表达进行了分析。随后,研究探讨了ECT2上调与肿瘤分期、分级和转移之间的相关性,以及其对患者生存的影响。
此外,还评估了ECT2在肿瘤与正常组织中的甲基化和磷酸化状态,并研究了ECT2对肿瘤微环境中免疫细胞浸润的影响。本研究发现,ECT2在一系列人类肿瘤中mRNA和蛋白水平均上调,这一特征使得髓源性抑制细胞(MDSC)的浸润增加,并降低了自然杀伤T(NKT)细胞水平,最终导致预后生存不良。
最后,我们筛选了若干可抑制ECT2并作为抗肿瘤药物的候选药物。总之,本研究将ECT2定位为一种预后和免疫生物标志物,并报道了代表潜在抗肿瘤药物的抑制剂。
Epithelial cell transforming 2 (ECT2) is a potential oncogene and a number of recent studies have correlated it with the progression of several human cancers. Despite this elevated attention for ECT2 in oncology-related reports, there is no collective study to combine and integrate the expression and oncogenic behavior of ECT2 in a panel of human cancers.
The current study started with a differential expression analysis of ECT2 in cancerous versus normal tissue. Following that, the study asked for the correlation between ECT2 upregulation and tumor stage, grade, and metastasis, along with its effect on patient survival.
Moreover, the methylation and phosphorylation status of ECT2 in tumor versus normal tissue was assessed, in addition to the investigation of the ECT2 effect on the immune cell infiltration in the tumor microenvironment. The current study revealed that ECT2 was upregulated as mRNA and protein levels in a list of human tumors, a feature that allowed for the increased filtration of myeloid-derived suppressor cells (MDSC) and decreased the level of natural killer T (NKT) cells, which ultimately led to a poor prognosis survival.
Lastly, we screened for several drugs that could inhibit ECT2 and act as antitumor agents. Collectively, this study nominated ECT2 as a prognostic and immunological biomarker, with reported inhibitors that represent potential antitumor drugs.
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