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高亲和力 IgE 受体在肺腺癌患者预后中的作用。

Role for High-Affinity IgE Receptor in Prognosis of Lung Adenocarcinoma Patients.

机构信息

Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada.

Department of Immunology, University of Toronto, Toronto, Ontario, Canada.

出版信息

Cancer Immunol Res. 2017 Sep;5(9):821-829. doi: 10.1158/2326-6066.CIR-16-0392. Epub 2017 Aug 3.

Abstract

Cancer development and biology is influenced by the host immune system. Emerging data indicate that the context of immune cell infiltrates may contribute to cancer prognosis. However, the types of infiltrating immune cells that are critical for cancer development remain controversial. In attempts to gain insights into the immune networks that regulate and/or predict tumor progression, gene expression analysis was conducted on microarray datasets of resected tumor samples from 128 early-stage non-small cell lung cancer (NSCLC) adenocarcinoma patients. By limiting analysis to immune-related genes, we identified a 9-gene signature using MAximizing R Square Algorithm that selected for the greatest separation between favorable and adverse prognostic patient subgroups. The prognostic value of this 9-gene signature was validated in 10 additional independently published microarray datasets of lung adenocarcinoma [ = 1,097; overall survival hazard ratio (HR), 2.05; 95% confidence interval, 1.64-2.56; < 0.0001] and was found to be an independent prognostic indicator relative to tumor stage (overall survival HR, 2.09, 95% confidence interval, 1.65-2.66; < 0.0001). Network analysis revealed that genes associated with Fcε complex () formed the largest and most significant pathway of the signature. Using immunohistochemistry, we validated that MS4A2, the β subunit of the IgE receptor expressed on mast cells, is a favorable prognostic indicator and show that MS4A2 gene expression is an independent prognostic marker for early-stage lung cancer patient survival. .

摘要

癌症的发生和生物学特性受宿主免疫系统的影响。新出现的数据表明,免疫细胞浸润的背景可能有助于癌症的预后。然而,对于促进癌症发生的浸润免疫细胞的类型仍存在争议。为了深入了解调节和/或预测肿瘤进展的免疫网络,我们对 128 例早期非小细胞肺癌(NSCLC)腺癌患者的切除肿瘤样本的微阵列数据集进行了基因表达分析。通过将分析仅限于免疫相关基因,我们使用最大平方算法(MAximizing R Square Algorithm)确定了一个 9 基因特征,该特征选择了有利于和不利于预后的患者亚组之间的最大分离。该 9 基因特征的预后价值在另外 10 个独立发表的肺腺癌微阵列数据集[=1097;总生存风险比(HR)为 2.05;95%置信区间为 1.64-2.56;<0.0001]中得到了验证,并发现其相对于肿瘤分期(总生存 HR,2.09,95%置信区间,1.65-2.66;<0.0001)是一个独立的预后指标。网络分析显示,与 Fcε 复合物()相关的基因形成了该特征的最大和最重要的途径。通过免疫组织化学,我们验证了 MS4A2(表达在肥大细胞上的 IgE 受体的 β 亚基)是一个有利的预后指标,并表明 MS4A2 基因表达是早期肺癌患者生存的独立预后标志物。

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