结肠腺癌中与 APC 和 TP53 相关的肿瘤微环境中的免疫格局:生物信息学分析。

European journal of microbiology & immunology Pub Date : 2024-03-12 Print Date: 2024-05-14 DOI:10.1556/1886.2024.00015
Arefeh Zabeti Touchaei, Sogand Vahidi, Ali Akbar Samadani
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引用次数: 0

摘要

简介APC和TP53是结肠腺癌(COAD)中最常发生突变的两个基因,特别是在进展期恶性肿瘤和抗肿瘤免疫反应中。目前的生物信息学分析研究了结肠腺癌中 APC 和 TP53 基因的表达谱,并将其作为预后生存的特征之一,尤其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对两组样本的基因差异表达进行分析。采用Kaplan-Meier生存曲线估算总生存期(OS)。P<0.05为差异有统计学意义。在肿瘤免疫估算资源和基因表达谱交互分析数据库中,通过斯皮尔曼相关分析评估了免疫细胞招募与APC和TP53状态之间的联系: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,分别有66.74%和85.71%的患者发现APC和TP53发生突变,与GTEx组(乙状结肠318例样本和横结肠368例样本)相比,每百万读数的对数2转录组更高。生存曲线显示,高 APC 和 TP53 特征结肠的显著 OS 更差。免疫细胞的斯皮尔曼分析表明,APC 状态与 T 细胞 CD4+、T 细胞 CD8+、NK 细胞和巨噬细胞的浸润呈强正相关,APC 状态与 T 细胞 CD4+、T 细胞 CD8+ 的浸润也呈正相关:结论:结肠癌中普遍存在 APC 和 TP53 基因突变,且与预后不良和最短生存期密切相关。浸润的 T 细胞 CD4+、T 细胞 CD8+、NK 细胞和巨噬细胞填充结肠微环境,调节肿瘤进展、免疫逃避和对标准化疗敏感性的机制。要证明这些结果并将其转化为新的治疗前景,还需要进行更全面的研究。
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Immune landscape in APC and TP53 related tumor microenvironment in colon adenocarcinoma: A bioinformatic analysis.

Introduction: APC and TP53 are the two most regularly mutated genes in colon adenocarcinoma (COAD), especially in progressive malignancies and antitumoral immune response. The current bioinformatics analysis investigates the APC and TP53 gene expression profile in colon adenocarcinoma as a prognostic characteristic for survival, particularly concentrating on the correlated immune microenvironment.

Methods: 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.

Results: 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+.

Conclusions: 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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