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:Angiotensin‑converting enzyme 2 as an immune and prognostic biomarker in colorectal cancer.
Angiotensin‑converting enzyme 2 as an immune and prognostic biomarker in colorectal cancer.
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血管紧张素转换酶2(ACE2)在某些癌症类型中被认为是一种致癌基因;然而,目前缺乏对ACE2在多种肿瘤类型中预后预测价值和免疫治疗反应作用的分析。
本研究利用癌症基因组图谱(TCGA)、肿瘤免疫估计资源(TIMER 2.0)、cBioPortal和ROC Plotter数据库的数据,分析了ACE2在多种肿瘤类型中的表达、预后和免疫细胞浸润情况。
此外,我们通过免疫组化分析研究了119对结直肠癌(CRC)组织中ACE2表达与临床病理特征的相关性,随后进行体外实验验证ACE2在CRC细胞迁移和增殖中的作用。
我们发现,与癌旁正常组织相比,ACE2在CRC组织中高表达,且ACE2表达水平高的CRC患者生存期较差。此外,结合生物信息学和qRT-PCR分析发现,ACE2表达与CRC中NK 细胞浸润呈强负相关。
同时,ACE2表达在抗CTLA-4和抗PD-L1治疗耐药患者中显著升高,并与不良预后相关。体外实验表明,沉默ACE2可抑制CRC细胞的增殖和侵袭。这些结果突出了ACE2在CRC发病机制和肿瘤-免疫相互作用中的参与,将其定位为CRC中有前景的预后和治疗生物标志物。
Angiotensin-converting enzyme 2 (ACE2) has been implicated as an oncogene in certain cancer types; however, there is a lack of analysis on the role of ACE2 in the predictive value for prognosis and immunotherapy response in various tumor types.
This study used data from the Cancer Genome Atlas (TCGA), Tumor Immune Estimation Resource (TIMER 2. 0), cBioPortal, and ROC Plotter databases to analyze the expression, prognosis, and immune cell infiltration of ACE2 in various tumor types.
Furthermore, we analyzed the correlation between the expression of ACE2 and clinicopathological characteristics in 119 pairs of colorectal cancer (CRC) tissues using immunohistochemistry analysis, and then conducted the in vitro experiments to verify the role of ACE2 in the migration and proliferation of CRC cells.
We found that ACE2 was highly expressed in CRC tissues compared with adjacent normal tissues, and that CRC patients with high ACE2 expression levels showed poor survival.
Additionally, combined bioinformatics and qRT-PCR analysis identified a strong negative correlation between ACE2 expression and natural killer cell infiltration in CRC. Meanwhile, ACE2 expression was significantly elevated in patients resistant to anti-CTLA-4 and anti-PD-L1 therapy and was linked to poor prognosis.
In vitro experiments showed that silencing ACE2 inhibits the proliferation and invasion of CRC cells. These results highlight ACE2's involvement in CRC pathogenesis and cancer-immune interactions, positioning it as a promising prognostic and therapeutic biomarker in CRC.
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