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:Immune landscape in APC and TP53 related tumor microenvironment in colon adenocarcinoma: A bioinformatic analysis.
Immune landscape in APC and TP53 related tumor microenvironment in colon adenocarcinoma: A bioinformatic analysis.
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APC 和 TP53 基因突变在结肠癌中普遍存在,并与不良预后和最短生存期密切相关。浸润性 T 细胞 CD4+、T 细胞 CD8+、NK 细胞和巨噬细胞填充结肠微环境,并调控肿瘤进展、免疫逃逸和对标准化疗敏感性的机制。需要更全面的研究来证实这些结果,并将其转化为新的治疗前景。
APC和TP53是结肠腺癌(COAD)中最常发生突变的两个基因,尤其是在进展性恶性肿瘤和抗肿瘤免疫反应中。当前的生物信息学分析探讨了APC和TP53基因表达谱在结肠腺癌中作为生存预后特征的作用,特别关注相关的免疫微环境。
结肠癌和正常组织样本的临床和遗传数据分别来自癌症基因组图谱(TCGA)-COAD和基因型-组织表达(GTEx)在线数据库。通过单因素方差分析检验分析两组中的遗传差异表达。采用Kaplan-Meier生存曲线评估总生存期(OS)。P < 0.05被确定为具有统计学意义。在肿瘤免疫估计资源和基因表达谱交互分析数据库中,通过Spearman相关分析评估免疫细胞募集与APC和TP53状态之间的关联。
在结肠和直肠乙状结肠交界原发部位的454例和7例TCGA-COAD患者中,分别发现APC和TP53的突变率为66.74%和85.71%,与GTEx组(乙状结肠318例样本和横结肠368例样本)相比,其每百万reads的log2转录组更高。生存曲线显示,高APC和TP53特征的结肠具有更差的显著OS。免疫细胞的Spearman分析表明,APC状态与T cell CD4+、T cell CD8+、NK cell和macrophages的浸润之间存在强正相关,并且状态与T cell CD4+、T cell CD8+的浸润之间也存在正相关。
Clinical and genetic data of colon cancer and normal tissue samples were obtained from The Cancer Genome Atlas (TCGA)-COAD and Genotype-Tissue Expression (GTEx) online databases, respectively. The genetic differential expressions were analyzed in both groups via the one-way ANOVA test. Kaplan-Meier survival curves were applied to estimate the overall survival (OS). P < 0.05 was fixed as statistically significant. On Tumor Immune Estimation Resource and Gene Expression Profiling Interactive Analysis databases, the linkage between immune cell recruitment and APC and TP53 status was assessed through Spearman's correlation analysis.
APC and TP53 were found mutated in 66.74% and 85.71% of the 454 and 7 TCGA-COAD patients in colon and rectosigmoid junction primary sites, respectively with a higher log2-transcriptome per million reads compared to the GTEx group (318 samples in sigmoid and 368 samples in transverse). Survival curves revealed a worse significant OS for the high-APC and TP53 profile colon. Spearman's analysis of immune cells demonstrated a strong positive correlation between the APC status and infiltration of T cell CD4+, T cell CD8+, NK cell, and macrophages and also a positive correlation between status and infiltration of T cell CD4+, T cell CD8+.
APC and TP53 gene mutations prevail in colon cancer and are extremely associated with poor prognosis and shortest survival. The infiltrating T cell CD4+, T cell CD8+, NK cell, and macrophages populate the colon microenvironment and regulate the mechanisms of tumor advancement, immune evasion, and sensitivity to standard chemotherapy. More comprehensive research is needed to demonstrate these results and turn them into new therapeutic outlooks.
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