Prognostic and Predictive Value of BGN in Colon Cancer Outcomes and Response to Immunotherapy.
Prognostic and Predictive Value of BGN in Colon Cancer Outcomes and Response to Immunotherapy.
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BGN 对结肠癌结果和免疫治疗反应的预后和预测价值
DOI：
10.3389/fonc.2021.761030
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发表时间：
2021
影响因子：
4.7
通讯作者：
Bai Y
中科院分区：
文献类型：
--
作者：
He ZX;Zhao SB;Fang X;E JF;Fu HY;Song YH;Wu JY;Pan P;Gu L;Xia T;Liu YL;Li ZS;Wang SL;Bai Y
结肠癌是最常见的恶性肿瘤之一，在全世界范围内导致高死亡率。探索肿瘤微环境中的肿瘤-免疫相互作用并鉴定新的预后和治疗生物标志物将有助于解码肿瘤免疫治疗的新机制。 BGN 是一种典型的细胞外基质蛋白，之前被验证为调节肿瘤发生多个过程的信号分子。然而，其在肿瘤免疫中的作用需要进一步研究。对三个GEO数据集中的差异表达基因进行分析，通过PPI交叉分析将BGN确定为目标基因。使用来自 GEO 数据库、TCGA 和结肠癌样本组织微阵列的数据评估临床结果和 BGN 表达水平之间的相关性。建立单变量和多变量Cox回归模型来确定与结肠癌患者临床预后相关的危险因素。接下来分析BGN表达水平与免疫细胞浸润以及免疫反应过程之间的关系。最后，我们通过 TIS 评分、ImmuCellAI 和 TIDE 算法预测了 BGN 低表达和高表达亚组的免疫治疗反应率。 BGN 表达在结肠癌组织中比在正常组织中表现出统计学上显着的上调。 BGN 升高与总生存期较短以及不利的临床病理特征（包括肿瘤大小、浆膜侵犯和住院时间）相关。从机制上讲，通路富集和功能分析表明，BGN 与 TME 中的免疫和基质评分呈正相关，并且主要参与免疫反应的调节。进一步研究发现，BGN在免疫抑制表型中强表达，并与结肠癌中多种免疫细胞，特别是M2巨噬细胞和诱导性Treg细胞的浸润密切相关。最后，我们证明高 BGN 表达在结肠癌患者中呈现出更好的免疫治疗反应。 BGN 是结肠癌患者诊断、预后和免疫治疗反应的一个令人鼓舞的预测因子。 BGN 表达的评估代表了一种新方法，对于识别可能从免疫治疗中受益的患者具有广阔的前景。
Colon cancer is one of the most frequent malignancies and causes high mortality worldwide. Exploring the tumor-immune interactions in the tumor microenvironment and identifying new prognostic and therapeutic biomarkers will assist in decoding the novel mechanism of tumor immunotherapy. BGN is a typical extracellular matrix protein that was previously validated as a signaling molecule regulating multiple processes of tumorigenesis. However, its role in tumor immunity requires further investigation. The differentially expressed genes in three GEO datasets were analyzed, and BGN was identified as the target gene by intersection analysis of PPIs. The relevance between clinical outcomes and BGN expression levels was evaluated using data from the GEO database, TCGA and tissue microarray of colon cancer samples. Univariable and multivariable Cox regression models were conducted for identifying the risk factors correlated with clinical prognosis of colon cancer patients. Next, the association between BGN expression levels and the infiltration of immune cells as well as the process of the immune response was analyzed. Finally, we predicted the immunotherapeutic response rates in the subgroups of low and high BGN expression by TIS score, ImmuCellAI and TIDE algorithms. BGN expression demonstrated a statistically significant upregulation in colon cancer tissues than in normal tissues. Elevated BGN was associated with shorter overall survival as well as unfavorable clinicopathological features, including tumor size, serosa invasion and length of hospitalization. Mechanistically, pathway enrichment and functional analysis demonstrated that BGN was positively correlated with immune and stromal scores in the TME and primarily involved in the regulation of immune response. Further investigation revealed that BGN was strongly expressed in the immunosuppressive phenotype and tightly associated with the infiltration of multiple immune cells in colon cancer, especially M2 macrophages and induced Tregs. Finally, we demonstrated that high BGN expression presented a better immunotherapeutic response in colon cancer patients. BGN is an encouraging predictor of diagnosis, prognosis and immunotherapeutic response in patients with colon cancer. Assessment of BGN expression represents a novel approach with great promise for identifying patients who may potentially benefit from immunotherapy.
DOI：
10.1155/2021/4812068
发表时间：
2021
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Liang B;Zheng B;Zhou Y;Lai ZQ;Zhang C;Yan Z;Li Z;Li X;Gong P;Qu J;Liu J
通讯作者：
Liu J