Knowledge Management System of Hefei Institute of Physical Science,CAS
Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis | |
Song, Zhengbo1,2; Yang, Ling3; Zhou, Zhipeng3; Li, Pansong3; Wang, Wenxian1; Cheng, Guoping2,4; Chen, Rongrong3; Chang, Lianpeng3; Zhang, Yiping1; Guan, Yanfang3; Xia, Xuefeng3; Yi, Xin3; Zhou, Rongrong5; Chen, Ming6 | |
2021-01-21 | |
发表期刊 | CELL DEATH & DISEASE |
ISSN | 2041-4889 |
通讯作者 | Song, Zhengbo(songzb@zjcc.org.cn) ; Zhou, Rongrong(zhourr@zjcc.org.cn) ; Chen, Ming(chenming@zjcc.org.cn) |
摘要 | Brain metastasis (BM) is a common malignant event in lung cancer. Here, we recruited 33 lung cancer patients with brain oligo-metastasis to explore the genomic features and tumor immune microenvironment (TIME) of the lung and BM independently. For genomic profiling, targeted sequencing was performed. We found that high-frequent ZFHX3 occurred in the lung (40%) and brain tumor (28%), which might relate to brain metastasis event; the vast majority of patients had lesions-shared mutations in primary tumor and BM, confirming the common clonal events; and EGFR was the most frequently clonal gene in both lung and BM, indicating its driver capability. To characterize TIME status, we also sequenced the T cell receptor (TCR) repertoires and performed immunohistochemistry (IHC) on CD8+ tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in 28 patients who had paired samples. Through the comparison, the TCR clonality of BM was higher than lung tumor, indicating the distinct pattern of the stronger oligoclonal T cell expansion in BM; the primary tumor had a higher TMB than oligo-BM (13.9 vs 8.7 mutations, p=0.019); CD8+TILs of BM were significantly lower than lung tumor (10% vs 30%, p=0.015), revealing the lower level of cytotoxic T cell infiltration; BM showed statistically equivalent level of PD-L1 compared with lung tumor (p=0.722). We further investigated the potential biomarkers associated with overall survival (OS) after brain surgery. We found that higher TCR clonality was related to prolonged OS in EGFR-treated patients (HR 0.175, p<0.001) but the worse outcomes in non-EGFR-treated (HR 2.623, p=0.034). More CD8+ TILs were an independently positive indicator for OS, in EGFR-treated (HR 0.160, p=0.001) and non-EGFR-treated patients (HR 0.308, p=0.009). These findings provide a meaningful molecular and clinical understanding of lung carcinoma and brain oligo-metastasis. |
DOI | 10.1038/s41419-021-03410-7 |
关键词[WOS] | CANCER ; MANAGEMENT ; SURGERY |
收录类别 | SCI |
语种 | 英语 |
资助项目 | National Natural Science Foundation of China[81802276] ; National Natural Science Foundation of China[81770928] ; Natural Science Foundation of Hunan[2018JJ2626] |
项目资助者 | National Natural Science Foundation of China ; Natural Science Foundation of Hunan |
WOS研究方向 | Cell Biology |
WOS类目 | Cell Biology |
WOS记录号 | WOS:000681135900002 |
出版者 | SPRINGERNATURE |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://ir.hfcas.ac.cn:8080/handle/334002/123073 |
专题 | 中国科学院合肥物质科学研究院 |
通讯作者 | Song, Zhengbo; Zhou, Rongrong; Chen, Ming |
作者单位 | 1.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Clin Trial, Hangzhou 310022, Zhejiang, Peoples R China 2.Chinese Acad Sci, Inst Basic Med & Canc, Hangzhou 310022, Zhejiang, Peoples R China 3.Geneplus Beijing Inst, Beijing 102206, Peoples R China 4.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Pathol, Hangzhou 310022, Zhejiang, Peoples R China 5.Cent South Univ, Xiangya Hosp, Dept Oncol, Changsha 410008, Hunan, Peoples R China 6.Univ Chinese Acad Sci, Zhejiang Canc Hosp, Canc Hosp, Dept Radiotherapy, Hangzhou 310022, Zhejiang, Peoples R China |
推荐引用方式 GB/T 7714 | Song, Zhengbo,Yang, Ling,Zhou, Zhipeng,et al. Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis[J]. CELL DEATH & DISEASE,2021,12. |
APA | Song, Zhengbo.,Yang, Ling.,Zhou, Zhipeng.,Li, Pansong.,Wang, Wenxian.,...&Chen, Ming.(2021).Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis.CELL DEATH & DISEASE,12. |
MLA | Song, Zhengbo,et al."Genomic profiles and tumor immune microenvironment of primary lung carcinoma and brain oligo-metastasis".CELL DEATH & DISEASE 12(2021). |
条目包含的文件 | 条目无相关文件。 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论