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基于下一代测序(NGS)检测的中国肺癌患者中不同亚型与PD-L1及肿瘤突变负荷(TMB)之间的关系。

The relationship between different subtypes of and PD-L1 & tumor mutation burden (TMB) based on next-generation sequencing (NGS) detection in Chinese lung cancer patients.

作者信息

Yang Ying, Shen Shengping, Sun Yingjia, Husain Hatim, Zhou Haiyan, Lu Shun, Li Ziming

机构信息

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

University of California San Diego, La Jolla, CA, USA.

出版信息

Transl Lung Cancer Res. 2022 Feb;11(2):213-223. doi: 10.21037/tlcr-22-88.

Abstract

BACKGROUND

gene mutations are the most common driver oncogenes in non-small cell lung cancer (NSCLC). We conducted an analysis of the immunological characteristics including tumor mutation burden and programmed death-ligand 1 (PD-L1) expression of different subtypes of in 2880 -mutant NSCLC patients.

METHODS

A total of 2,880 patients with NSCLC were included in the study. Somatic mutation data were provided by Berry Oncology (Fujian, China), Geneplus BioTech (Beijing, China), Nanjing Geneseeq Technology Inc (Nanjing, China), and Burning Rock Biotech (Guangzhou, China). Z-scores were used to unify all data. SPSS 20.0 (SPSS, Chicago, IL, USA) software was used for statistical analyses. All scatter plots and boxplot maps were drawn using GraphPad Prism 8. Tumor mutation burden (TMB) expression was defined by the number of somatic mutations. The PD-L1 clone 22C3 pharmDx kit was used to measure the expression level of PD-L1. Mann-Whitney U test was used for statistical analysis. P value <0.05 was considered statistically significant.

RESULTS

We identified 2,880 patients with -mutant NSCLC. The percentage level of TMB and expression of PD-L1 was significantly decreased in -mutant lung cancer tissue and blood samples (n=162). The percentage level of TMB and expression of PD-L1 in -mutant lung cancer specimens was significantly increased (n=190).

CONCLUSIONS

The findings demonstrate a decreased level of TMB and expression of PD-L1 in -mutant lung cancer and the increased level of TMB and expression of PD-L1 in -mutant lung cancer. Further work is needed to identify if the subtype of mutation could be a potential therapeutic biomarker in lung cancer patients with mutation. TMB data was consistently verified in tissue and blood samples and confirmed the feasibility of next-generation sequencing (NGS) verification in plasma samples. Our research may help to provide more individualized treatment options for NSCLC patients.

摘要

背景

基因突变是非小细胞肺癌(NSCLC)中最常见的驱动癌基因。我们对2880例 - 突变型NSCLC患者不同亚型的免疫特征进行了分析,包括肿瘤突变负荷和程序性死亡配体1(PD-L1)表达。

方法

本研究共纳入2880例NSCLC患者。体细胞突变数据由贝瑞基因(中国福建)、吉因加生物科技(中国北京)、南京世和基因生物技术有限公司(中国南京)和燃石医学(中国广州)提供。使用Z分数对所有数据进行统一。采用SPSS 20.0(美国伊利诺伊州芝加哥市SPSS公司)软件进行统计分析。所有散点图和箱线图均使用GraphPad Prism 8绘制。肿瘤突变负荷(TMB)表达由体细胞突变数量定义。使用PD-L1克隆22C3检测试剂盒测量PD-L1表达水平。采用Mann-Whitney U检验进行统计分析。P值<0.05被认为具有统计学意义。

结果

我们鉴定出2880例 - 突变型NSCLC患者。 - 突变型肺癌组织和血液样本(n = 162)中TMB百分比水平和PD-L1表达显著降低。 - 突变型肺癌标本中TMB百分比水平和PD-L1表达显著升高(n = 190)。

结论

研究结果表明, - 突变型肺癌中TMB水平和PD-L1表达降低,而 - 突变型肺癌中TMB水平和PD-L1表达升高。需要进一步研究以确定 突变亚型是否可能成为 突变肺癌患者的潜在治疗生物标志物。TMB数据在组织和血液样本中得到一致验证,并证实了血浆样本中下一代测序(NGS)验证的可行性。我们的研究可能有助于为NSCLC患者提供更多个性化治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19a8/8902092/17191c710113/tlcr-11-02-213-f1.jpg

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