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:Clinical significance of KRT7 in bladder cancer prognosis.
Clinical significance of KRT7 in bladder cancer prognosis.
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KRT7 作为生物标志物增强了对膀胱癌预后和免疫微环境的预测。
通常,过表达的角蛋白7(KRT7)被认为是膀胱癌中经过验证的治疗靶点和预后标志物。然而,KRT7在膀胱癌临床预后和免疫微环境中的关键作用仍不清楚。
首先,分析公共数据库中KRT7的表达水平,即肿瘤免疫估计资源(TIMER)2.0和基因表达谱交互分析(GEPIA)。进一步,收集患者的临床组织样本(n = 10对),通过免疫组织化学(IHC)分析检测以确认KRT7的表达趋势。同时,通过Kaplan-Meier绘图估计和Cox回归分析,分析KRT7与膀胱癌患者预后之间的关系。最后,进行TIMER 2.0和IHC染色分析,以计算合格膀胱肿瘤样本中三种免疫细胞的浸润丰度。
TIMER 2.0和GEPIA数据集提示肿瘤中KRT7表达水平的差异,其中KRT7在膀胱癌中显著上调。KRT7表达与患者性别、肿瘤组织学亚型、T状态和美国癌症联合委员会分期密切相关。值得注意的是,KRT7升高提示总生存率和无病生存率较差。此外,KRT7表达可能与膀胱癌症微环境中的免疫浸润有关。最后,KRT7的高表达水平增加了调节性T细胞(Tregs)的存在,但减少了CD8+ T细胞和NK 细胞的浸润。
Typically, the overexpressed keratin 7 (KRT7) is considered a validated therapeutic target and prognosis marker in bladder cancer. However, the crucial roles of KRT7 in the clinical prognosis and immune microenvironment in bladder cancer remain unclear.
Initially, the expression levels of KRT7 in public databases were analyzed that is,Tumor Immune Estimation Resource (TIMER) 2.0 and Gene Expression Profiling Interactive Analysis (GEPIA). Further, the clinical tissue samples from patients (n = 10 pairs) were collected to confirm the expression trends of KRT7 and detected by immunohistochemistry (IHC) analysis. Meanwhile, the relationship between KRT7 and the prognosis of bladder cancer patients was analyzed by Kaplan-Meier plotter estimation and Cox regression analysis. Finally, TIMER 2.0 and IHC staining analyses were performed to calculate the infiltration abundances of three kinds of immune cells in eligible bladder tumor samples.
The TIMER 2.0 and GEPIA datasets suggested the differences in the expression levels of KRT7 in tumors, in which KRT7 was significantly upregulated in bladder cancer. The KRT7 expression was closely associated with patients' gender, tumor histologic subtypes, T status, and American Joint Committee on Cancer stages. Notably, the increased KRT7 indicated poor overall survival and disease-free survival rates. Moreover, KRT7 expression could be responsible for immune infiltration in the cancer microenvironment of the bladder. Finally, the high expression level of KRT7 increased the presence of regulatory T cells (Tregs) but reduced the infiltration of CD8+ T and natural killer cells.
KRT7 as a biomarker potentiated the prediction of bladder cancer prognosis and the immune microenvironment.
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