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Evaluating the Potential of T Cell Receptor Repertoires in Predicting the Prognosis of Resectable Non-Small Cell Lung Cancers
Molecular Therapy - Methods & Clinical Development ( IF 4.7 ) Pub Date : 2020-05-22 , DOI: 10.1016/j.omtm.2020.05.020
Zhengbo Song , Xiangbin Chen , Yi Shi , Rongfang Huang , Wenxian Wang , Kunshou Zhu , Shaofeng Lin , Minxian Wang , Geng Tian , Jialiang Yang , Gang Chen

For resectable cancer patients, a method that could precisely predict the risk of postoperative recurrence would be crucial for guiding adjuvant treatment. Since T cell receptor (TCR) repertoires had been shown to be closely related to the dynamics of cancers, here we enrolled a cohort of patients to evaluate the potential of TCR repertoires in predicting the prognosis of resectable non-small cell lung cancers. Specifically, TCRβ repertoires were analyzed in surgical tumor tissues and matched adjacent non-tumor tissues from 39 patients enrolled with resectable non-small cell lung cancer, through target enrichment and high-throughput sequencing. As a result, there are significant differences between the TCR repertories of tumor samples and those of matched adjacent non-tumor samples as evaluated by criteria like the number of clonotypes. In addition, TCR repertoires were significantly associated with a few clinical features, as well as somatic mutations. Finally, certain TCRβ variable-joining (V-J) pairings were featured to build a logistic regression model in predicting postoperative recurrence of resectable non-small cell lung cancers with a testing area under the receiver operating characteristic curve (AUC) of around 0.9. Thus, we hypothesize that TCR repertoires could be potentially used to predict prognosis after curative surgery for non-small cell lung cancer patients.



中文翻译:

评价T细胞受体库在预测可切除的非小细胞肺癌预后中的潜力

对于可切除的癌症患者,一种能够准确预测术后复发风险的方法对于指导辅助治疗至关重要。由于已显示T细胞受体(TCR)的库与癌症的动力学密切相关,因此我们招募了一批患者来评估TCR库在预测可切除的非小细胞肺癌的预后中的潜力。具体而言,通过靶标富集和高通量测序分析了39例可切除的非小细胞肺癌患者的手术肿瘤组织和匹配的相邻非肿瘤组织中的TCRβ组成。结果,如克隆标准数目之类的标准所评估,肿瘤样品的TCR库与匹配的相邻非肿瘤样品的TCR库之间存在显着差异。另外,TCR库与一些临床特征以及体细胞突变显着相关。最后,某些TCRβ可变连接(VJ)配对的特征是建立了Logistic回归模型,以预测可切除的非小细胞肺癌的术后复发,受试者工作特征曲线(AUC)下的测试面积约为0.9。因此,我们假设TCR的所有组成可能可用于预测非小细胞肺癌患者根治性手术后的预后。某些TCRβ可变连接(VJ)配对的特征是建立了Logistic回归模型,以预测可切除的非小细胞肺癌的术后复发,受试者工作特征曲线(AUC)下的测试面积约为0.9。因此,我们假设TCR的所有组成可能可用于预测非小细胞肺癌患者治愈性手术后的预后。某些TCRβ可变连接(VJ)配对的特征是建立了Logistic回归模型,以预测可切除的非小细胞肺癌的术后复发,受试者工作特征曲线(AUC)下的测试面积约为0.9。因此,我们假设TCR的所有组成可能可用于预测非小细胞肺癌患者治愈性手术后的预后。

更新日期:2020-06-19
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