Analysis of tumor-related features of non-small cell lung cancer based on TCR repertoire workflow
10.3969/j.issn.1674-8115.2023.12.006
- VernacularTitle:基于TCR组库分析流程的非小细胞肺癌特征分析
- Author:
Zhuoming ZHAO
1
,
2
;
Zhenhao LIU
;
Manman LU
;
Yu ZHANG
;
Linfeng XU
;
Lu XIE
Author Information
1. 上海海洋大学食品学院食品科学与工程学科(系),上海 201306
2. 上海市生物医药技术研究院基因组与生物信息研究所,上海市疾病与健康基因组学重点实验室,上海 200237
- Keywords:
T cell receptor(TCR);
TCR repertoire;
tumor immunity;
non-small cell lung cancer(NSCLC)
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2023;43(12):1520-1528
- CountryChina
- Language:Chinese
-
Abstract:
Objective·To explore the immune-related characteristics of non-small cell lung cancer(NSCLC),discover potential tumor markers in V-J genes,and lay the foundation for establishing a TCR-antigen recognition prediction model.Methods·A total of 704 NSCLC samples were collected to establish a comprehensive T-cell receptor(TCR)repertoire analysis workflow.The upstream analysis included steps such as raw data processing,quality control,filtering,TCR sequence identification,and extraction.The downstream analysis included repertoire clone distribution,clone typing,V-J gene sharing,CDR3 distribution characteristics,and clone tracking.The sample clone distribution was analyzed by using indices such as Shannon-Weiner index and Chaol index.Clone typing was performed based on the number of clone amplifications to explore differences among different types.The degree of V-J gene segment sharing was analyzed,and the sharing of low-frequency clone types was determined through clone amplification weight analysis of V-J genes by using two samples of papillary thyroid carcinoma.Finally,analysis of the distribution characteristics of V genes and high-frequency clone type CDR3,and clone tracking analysis were conducted to monitor changes in tumor immune clone frequencies before and after analysis,aiming to identify potential tumor markers.Results·① Significant differences were observed in clone distribution and clone typing among different NSCLC tissues,as well as among different ages and genders.② Specific highly-shared V-J genes were identified in the analysis of V-J gene sharing,and non-normal distribution of high-clone V genes and amino acid high-frequency clone types were found in the CDR3 distribution analysis.③ In the analysis of high-frequency clone type clone tracking,highly expressed or newly expressed high-frequency clone types were observed in NSCLC,suggesting that these clone types could serve as potential tumor-associated antigens or bind with CDR3 reference sequences of new antigens.④ It was found that the expression frequency of TRBJ2-5 gene,originally low-expressed,significantly increased,indicating its potential role as a key low-frequency gene in tumor immune response.Conclusion·The TRAV21 and TRBV6.5 genes show high clone amplification in NSCLC and could serve as potential tumor biomarkers.
