Yuan Wei, Yan Jiaqin, Liu Hongtao, Li Ling, Wu BoWen, Guo Can, Zhang Mingzhi
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Pathol Oncol Res. 2021 Apr 1;27:589662. doi: 10.3389/pore.2021.589662. eCollection 2021.
Esophageal cancer (ESCA) is a commonly occurring cancer worldwide with poor survival and limited therapeutic options. Due to the lack of biomarkers that facilitate early detection, its treatment remains a great challenge. This study aims at identifying the tumor microenvironment (TME)-related genes, which might affect prognosis and accelerate clinical treatment for ESCA patients. We integrated the expression profiles from ESCA patients in The Cancer Genome Atlas. Then, we determined the stromal and immune scores of each sample using the R package. The Gene Expression Omnibus database was used to validate the expression profile of the key genes. Tumor mutational burden showed a significant difference between the groups of ESCA patients with high and low ESTIMATE scores. We identified 859 intersection genes among patients with different immune and stromal scores. Moreover, gene ontology analysis demonstrated that these 859 intersection genes were closely related to adaptive immune response and regulation of lymphocyte activation. Kyoto Encyclopedia of Genes and Genomes showed the enrichment of cytokine-cytokine receptor interaction and chemokine signaling pathway in the TME. Furthermore, the protein-protein interaction network consisted of 175 nodes. We selected 35 hub genes, including ITGAM, CXCL10, CCR2, CCR5, and CCR1. Of these, 23 intersection genes predicted the overall survival rate. C1QA and FCER1G correlated with overall survival of the ESCA patients in the two databases. We identified a set of stromal and immune score-related prognostic differentially expressed genes that could influence the complexity of the TME. C1QA and FCER1G were identified and validated with respect to their role in the progression of ESCA.
食管癌(ESCA)是全球常见的癌症,生存率低且治疗选择有限。由于缺乏有助于早期检测的生物标志物,其治疗仍然是一个巨大的挑战。本研究旨在识别可能影响食管癌患者预后并加速临床治疗的肿瘤微环境(TME)相关基因。我们整合了癌症基因组图谱中食管癌患者的表达谱。然后,我们使用R包确定每个样本的基质和免疫评分。利用基因表达综合数据库验证关键基因的表达谱。肿瘤突变负担在高ESTIMATE评分和低ESTIMATE评分的食管癌患者组之间存在显著差异。我们在具有不同免疫和基质评分的患者中鉴定出859个交集基因。此外,基因本体分析表明,这859个交集基因与适应性免疫反应和淋巴细胞激活调节密切相关。京都基因与基因组百科全书显示TME中细胞因子-细胞因子受体相互作用和趋化因子信号通路的富集。此外,蛋白质-蛋白质相互作用网络由175个节点组成。我们选择了35个枢纽基因,包括整合素αM(ITGAM)、趋化因子CXCL10、趋化因子受体2(CCR2)、趋化因子受体5(CCR5)和趋化因子受体1(CCR1)。其中,23个交集基因可预测总生存率。补体C1q亚基A(C1QA)和高亲和力IgE受体γ链(FCER1G)在两个数据库中均与食管癌患者的总生存率相关。我们鉴定出一组与基质和免疫评分相关的预后差异表达基因,它们可能影响TME的复杂性。鉴定并验证了C1QA和FCER1G在食管癌进展中的作用。