USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma.
USH2A Mutation is Associated With Tumor Mutation Burden and Antitumor Immunity in Patients With Colon Adenocarcinoma.
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DOI：
10.3389/fgene.2021.762160
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发表时间：
2021
影响因子：
3.7
通讯作者：
Xue D
中科院分区：
文献类型：
--
作者：
Sun Y;Li L;Yao W;Liu X;Yang Y;Ma B;Xue D
结肠腺癌是世界上发病率和死亡率最高的疾病之一。目前，免疫治疗已成为治疗慢性阻塞性肺疾病的有价值的方法。肿瘤突变负荷(TMB)被认为是预测免疫治疗的最常见的生物标志物。据报道，Coad的突变率位居第三。然而，这些基因突变是否与TMB和免疫反应有关尚不清楚。在这里，Coad体细胞突变数据是从癌症基因组图谱(TCGA)和国际癌症基因组联合会(ICGC)数据库下载的。应用生物信息学方法研究基因突变、COAD生存预后和肿瘤免疫应答之间的关系。在TCGA和ICGC数据库中，前40个突变中共有22个是相同的。其中，USH2A突变与TMB升高和临床预后不良有关。根据基因集浓缩分析(GSEA)和CiberSort算法，我们确定USH2A突变上调了参与免疫系统和抗肿瘤免疫反应的信号通路。在USH2A突变的病例中，TCGA样本的免疫评分和MSI评分升高，免疫检查点基因的表达显著下降，TEDGE评分显著下降。根据USH2A突变的存在与否，对TCGA Coad样本进行了差异表达基因的分析，其中522个基因被鉴定。对这些差异基因进行单因素Cox分析和套索Cox分析，建立预测模型，发现高危组和低危组患者在免疫细胞浸润、免疫检查点基因表达、免疫评分、MSI评分、TMB和TID等方面存在显著差异。综上所述，USH2A基因突变在CoAD中较为常见，并与TMB的升高和抗肿瘤免疫有关。通过USH2A突变筛选出的差异基因，不仅可以构建预测癌症患者生存和预后的风险模型，还可以为Coad免疫治疗提供新的思路。
Colon adenocarcinoma (COAD) is one of the diseases with the highest morbidity and mortality in the world. At present, immunotherapy has become a valuable method for the treatment of COAD. Tumor mutational burden (TMB) is considered to be the most common biomarker for predicting immunotherapy. According to reports, the mutation rate of COAD ranks third. However, whether these gene mutations are related to TMB and immune response is still unknown. Here, COAD somatic mutation data were downloaded from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Bioinformatics methods were used to study the relationships among gene mutations, COAD survival prognosis, and tumor immune response. A total of 22 of the top 40 mutations in TCGA and ICGC databases were the same. Among them, the USH2A mutation was associated with high TMB and poor clinical prognosis. According to Gene Set Enrichment Analysis (GSEA) and the CIBERSORT algorithm, we determined that the USH2A mutation upregulates signaling pathways involved in the immune system and the antitumor immune response. In cases with a USH2A mutation, the immune score and MSI score of TCGA samples increased, the expression of immune checkpoint genes decreased significantly, and the TIDE score decreased significantly. Dependent on the presence or absence of a USH2A mutation, TCGA COAD samples were analyzed for differentially expressed genes, 522 of which were identified. Using a univariate Cox analysis and LASSO COX analysis of these differential genes, a prediction model was established, which established significant differences in the infiltration of immune cells, immune checkpoint gene expression, immune score, MSI score, TMB, and TIDE in patients in high- and low-risk groups. In conclusion, mutation of USH2A is frequent in COAD and is related to an increase in TMB and the antitumor immunity. The differential genes screened by USH2A mutation allowed the construction of a risk model for predicting the survival and prognosis of cancer patients, in addition to providing new ideas for COAD immunotherapy.
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