Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
Department of Organ Transplantation and Hepatobiliary, the First Affiliated Hospital of China Medical University, Shenyang, China.
Front Immunol. 2022 Feb 16;13:809837. doi: 10.3389/fimmu.2022.809837. eCollection 2022.
EVA1B, a protein coding gene, is a critical paralog of EVA1A gene. Herein, our study was conducted to investigate the role of EVA1B in colorectal cancer (CRC) progression and prognosis.
Pan-cancer analysis was conducted to analyze expression, genetic and epigenetic alterations, and immunological characteristics of EVA1B. Especially, immunological characteristics and mutational landscape were compared between high and low EVA1B expression groups in the combined TCGA-COAD and TCGA-READ datasets. Through random survival forest analysis, an EVA1B-derived genomic model was developed, and its prognostic value was verified in the external datasets (GSE14333, GSE39582, and GSE87211). Drug sensitivity was compared between high- and low-risk subpopulations. A nomogram was conducted through integrating independent factors.
EVA1B expression presented a remarkable upregulation in most cancer types, especially CRC. EVA1B expression was significantly correlated to DNA methyltransferases, DNA mismatch repair genes, mA regulators, TMB, and MSI across pan-cancer. High EVA1B expression indicated an undesirable CRC patients' prognosis. Additionally, its upregulation was correlated to enhanced immune cell infiltration, increased stromal and immune activation, and elevated activities of cancer immunity cycle. Higher frequencies of amplification and deletion were investigated in high EVA1B expression subpopulation. Following verification, the EVA1B-derived genomic model reliably predicted patients' prognosis and drug responses. The nomogram (age, stage, EVA1B-derived risk score) was conducted to quantify an individual's survival probability. Furthermore, our experimental validation based on immunohistochemistry indicated that EVA1B overexpression is correlated with CRC tumorigenesis and poor outcomes in our CRC patients' cohort.
Collectively, our findings provided valuable resource for guiding the mechanisms and therapeutic analysis of EVA1B in CRC.
EVA1B 是一种蛋白质编码基因，是 EVA1A 基因的关键同源基因。在此，我们研究了 EVA1B 在结直肠癌（CRC）进展和预后中的作用。
进行泛癌分析，以分析 EVA1B 的表达、遗传和表观遗传改变以及免疫学特征。特别是，在联合 TCGA-COAD 和 TCGA-READ 数据集比较了 EVA1B 高表达和低表达组之间的免疫学特征和突变景观。通过随机生存森林分析，建立了一个基于 EVA1B 的基因组模型，并在外部数据集（GSE14333、GSE39582 和 GSE87211）中验证了其预后价值。比较高风险和低风险亚群之间的药物敏感性。通过整合独立因素，构建了一个列线图。
EVA1B 表达在大多数癌症类型中均显著上调，尤其是 CRC。EVA1B 表达与 DNA 甲基转移酶、DNA 错配修复基因、mA 调节剂、TMB 和 MSI 在泛癌中均显著相关。EVA1B 高表达提示 CRC 患者预后不良。此外，EVA1B 的上调与增强的免疫细胞浸润、增加的基质和免疫激活以及提高的癌症免疫周期活性相关。在 EVA1B 高表达亚群中观察到更高的扩增和缺失频率。经过验证，基于 EVA1B 的基因组模型可可靠预测患者的预后和药物反应。列线图（年龄、分期、EVA1B 衍生风险评分）用于量化个体的生存概率。此外，我们基于免疫组织化学的实验验证表明，EVA1B 的过表达与我们 CRC 患者队列中的 CRC 肿瘤发生和不良结局相关。
总之，我们的研究结果为指导 EVA1B 在 CRC 中的机制和治疗分析提供了有价值的资源。
