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:The expression of ERAP1 is favorable for the prognosis and immunotherapy in colorectal cancer: a study based on the bioinformatic and immunohistochemical analysis.
The expression of ERAP1 is favorable for the prognosis and immunotherapy in colorectal cancer: a study based on the bioinformatic and immunohistochemical analysis.
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ERAP1 具有作为诊断和预后生物标志物的潜力,为 CRC 研究和有效疗法的设计提供了新的见解。
内质网氨肽酶1(ERAP1)是癌症免疫治疗中一个新出现的药理学靶点。本研究旨在探讨ERAP1在CRC中的表达谱及其对预后和免疫治疗的意义。
基于生物信息学和免疫组化分析,我们分析了ERAP1在CRC中的潜在诊断和预后意义。进行功能富集分析以检测与ERAP1相关的通路,从而确定可能的机制。ESTIMATE、TIMER和CIBESORT探究了ERAP1与肿瘤浸润免疫细胞之间的联系。最后,我们检验了ERAP1表达与免疫治疗敏感性的相关性。
肿瘤组织中ERAP1表达水平较正常组织降低。ERAP1低表达患者的生存机会更差。此外,研究显示ERAP1表达与晚期M分期和病理分期相关。生存分析显示,ERAP1低表达、年龄、病理分期、T分期和M分期是CRC患者不良预后的独立指标。1年、3年和5年OS校准曲线均与理想模型拟合良好,表明年龄-ERAP1-T分期-M分期列线图是OS的可靠预测因子。此外,我们发现ERAP1表达与免疫反应及多种免疫细胞的浸润相关,如下调抑制性免疫细胞和上调刺激性免疫细胞。对PD-1和CTLA4抑制剂的敏感性也与高ERAP1水平相关。
Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an emerging pharmacological target in cancer immunotherapy. This study was set out to examine the expression profiles and implications for prognosis and immunotherapy of ERAP1 in CRC.
Based on bioinformatics and immunohistochemical analysis, we analyzed ERAP1 for potential diagnostic and prognostic significance in CRC. Functional enrichment analysis was conducted to detect the pathways associated with ERAP1, thus determining possible mechanisms. ESTIMATE, TIMER, and CIBESORT probed the links between ERAP1 and tumor-infiltrating immune cells. Lastly, we examined how ERAP1 expression correlated with the sensitivity to immunotherapy.
Tumor tissues had decreased levels of ERAP1 expression relative to normal tissues. Patients whose ERAP1 expression was low suffered a worse chance of survival. Besides, it was shown that ERAP1 expression was associated with the advanced M stage and pathologic stage. Survival analysis revealed that low ERAP1 expression, age, pathologic stage, T stage, and M stage were independent indicators for unfavorable CRC patients' prognoses. The 1-, 3-, and 5-year OS calibration curves all fit well with the ideal model, suggesting that the age-ERAP1-T-stage-M-stage nomogram is a reliable predictor of OS. Additionally, we discovered that ERAP1 expression was associated with immune response and infiltration of various immune cells, such as down-regulated inhibitory immune cells and up-regulated stimulating immune cells. Sensitivity to PD-1 and CTLA4 inhibitors was associated with high ERAP1 levels.
In summary, ERAP1 has potential as a diagnostic and prognostic biological marker, highlighting new insights into the study of CRC and the design of effective therapies.
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