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:Chemokines as Prognostic Factor in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.
Chemokines as Prognostic Factor in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis.
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趋化因子在肿瘤发生过程的许多方面发挥协调作用,如血管生成、凋亡和转移扩散,相关受体表达于肿瘤细胞以及肿瘤微环境中的炎症细胞(例如肿瘤浸润性T细胞,TILs)。趋化因子及其受体在实体癌中的表达变化是常见且众所周知的,尤其是在影响结直肠癌患者预后方面。
因此,本系统综述和荟萃分析旨在将趋化因子归类为结直肠癌患者的预后生物标志物。在PubMed、CENTRAL和Web of Science中进行了系统性文献检索。研究了结直肠癌组织中25种趋化因子的表达信息以及患者的生存数据。检查了趋化因子表达与总生存期和无病生存期的风险比。使用预后研究质量工具分析偏倚风险。进行随机效应荟萃分析以确定对总生存期和疾病生存期的影响。为此,使用汇总风险比(HR)及其95%置信区间(CI)进行计算。共纳入25种趋化因子,检索发现5556篇文献。本系统综述和荟萃分析共纳入31篇文献。趋化因子受体CXCR4过表达与总生存期显著降低(HR = 2.70,95%-CI:1.57至4.66,p = 0.0003)以及无病生存期显著降低(HR = 2.68,95%-CI:1.41至5.08,p = 0.0026)均相关。所有其他趋化因子显示结果异质性较大或可用研究较少。CXCR4的总体偏倚风险被评为低。在目前的证据水平下,本研究表明结直肠癌患者中CXCR4过表达与总生存期及无病生存期显著缩短相关。
综上所述,本系统评价和meta分析揭示CXCR4是一个有前景的预后生物标志物。然而,仍需更多证据来评估CXCR4及其拮抗剂作为新治疗靶点的价值。
Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e. g. , tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes.
Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications.
A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2. 70, 95%-CI: 1. 57 to 4. 66, p = 0. 0003) as well as disease-free survival (HR = 2. 68, 95%-CI: 1. 41 to 5. 08, p = 0. 0026). All other chemokines showed either heterogeneous results or few studies were available.
The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets.
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