Zabeti Touchaei Arefeh, Vahidi Sogand, Samadani Ali Akbar
1Department of Chemistry, Lahijan Branch, Islamic Azad University, Lahijan, Iran.
2Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Eur J Microbiol Immunol (Bp). 2024 Mar 12;14(2):154-165. doi: 10.1556/1886.2024.00015. Print 2024 May 14.
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.
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.
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研究了结肠腺癌中APC和TP53基因表达谱作为生存的预后特征,特别关注相关的免疫微环境。
分别从癌症基因组图谱(TCGA)-COAD和基因型-组织表达(GTEx)在线数据库中获取结肠癌和正常组织样本的临床和基因数据。通过单向方差分析测试分析两组中的基因差异表达。应用Kaplan-Meier生存曲线来估计总生存期(OS)。将P < 0.05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上,通过Spearman相关性分析评估免疫细胞募集与APC和TP53状态之间的联系。
在结肠和直肠乙状结肠交界处原发部位的454例和7例TCGA-COAD患者中,分别发现66.74%和85.71%的患者发生APC和TP53突变,与GTEx组(乙状结肠318个样本和横结肠368个样本)相比,每百万读取中log2转录组更高。生存曲线显示,高APC和TP53表达谱的结肠癌患者的OS明显更差。Spearman免疫细胞分析表明,APC状态与T细胞CD4 +、T细胞CD8 +、NK细胞和巨噬细胞的浸润之间存在强正相关,并且与T细胞CD4 +、T细胞CD8 +的状态和浸润之间也存在正相关。
APC和TP53基因突变在结肠癌中普遍存在,并且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细胞和巨噬细胞构成结肠微环境,并调节肿瘤进展、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。