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评估T细胞受体库在预测可切除非小细胞肺癌预后中的潜力

Evaluating the Potential of T Cell Receptor Repertoires in Predicting the Prognosis of Resectable Non-Small Cell Lung Cancers.

作者信息

Song Zhengbo, Chen Xiangbin, Shi Yi, Huang Rongfang, Wang Wenxian, Zhu Kunshou, Lin Shaofeng, Wang Minxian, Tian Geng, Yang Jialiang, Chen Gang

机构信息

Department of Medical Oncology, Cancer Hospital of University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, China.

Geneis Beijing, Beijing 100102, China.

出版信息

Mol Ther Methods Clin Dev. 2020 May 22;18:73-83. doi: 10.1016/j.omtm.2020.05.020. eCollection 2020 Sep 11.

Abstract

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.

摘要

对于可切除癌症患者而言,一种能够精确预测术后复发风险的方法对于指导辅助治疗至关重要。由于已表明T细胞受体(TCR)库与癌症动态密切相关,因此我们招募了一组患者,以评估TCR库在预测可切除非小细胞肺癌预后方面的潜力。具体而言,通过靶向富集和高通量测序,对39例可切除非小细胞肺癌患者的手术肿瘤组织及配对的相邻非肿瘤组织中的TCRβ库进行了分析。结果显示,根据克隆型数量等标准评估,肿瘤样本与配对的相邻非肿瘤样本的TCR库存在显著差异。此外,TCR库与一些临床特征以及体细胞突变显著相关。最后,某些TCRβ可变区连接(V-J)配对被用于构建逻辑回归模型,以预测可切除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,我们推测TCR库可能潜在地用于预测非小细胞肺癌患者根治性手术后的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f49/7488751/8f88ec4ec313/fx1.jpg

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