State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Division of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Sci Rep. 2017 Aug 10;7(1):7762. doi: 10.1038/s41598-017-08289-z.
Many basic properties of the T-cell receptor (TCR) repertoire require clarification, and the changes occurring in the TCR repertoire during carcinogenesis, especially during precancerous stages, remain unclear. This study used deep sequencing analyses to examine 41 gastric tissue samples at different pathological stages, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, early gastric cancer and matched adjacent tissues, to define the characteristics of the infiltrating TCRβ repertoire during gastric carcinogenesis. Moreover, to illustrate the relationship between the local molecular phenotype and TCR repertoire of the microenvironment, whole-genome gene expression microarray analysis of the corresponding gastric precancerous lesions and early gastric cancer tissues was conducted. Our results showed that the degree of variation in the TCR repertoire gradually increased during tumourigenesis. Integrative analysis of microarray data and the TCR repertoire variation index using the network-based Clique Percolation Method identified an 11-gene module related to the inflammatory response that can predict the overall survival of gastric cancer (GC) patients. In conclusion, our results revealed the multistage heterogeneity of tissue-infiltrating TCR repertoire during carcinogenesis. We report a novel way for identifying prognostic biomarkers for GC patients and improves our understanding of immune responses during gastric carcinogenesis.
许多 T 细胞受体 (TCR) 库的基本特性尚需阐明，特别是在癌前阶段，TCR 库在癌变过程中发生的变化仍不清楚。本研究采用深度测序分析方法，检测了 41 个不同病理阶段的胃组织样本，包括低级别上皮内瘤变、高级别上皮内瘤变、早期胃癌和匹配的相邻组织，以确定胃癌变过程中浸润性 TCRβ库的特征。此外，为了阐明微环境中局部分子表型与 TCR 库之间的关系，对相应的胃癌前病变和早期胃癌组织进行了全基因组基因表达微阵列分析。我们的结果表明，TCR 库的变异程度在肿瘤发生过程中逐渐增加。使用基于网络的团块渗滤方法对微阵列数据和 TCR 库变异指数进行综合分析，确定了与炎症反应相关的 11 个基因模块，该模块可预测胃癌 (GC) 患者的总生存率。总之，我们的研究结果揭示了癌变过程中组织浸润性 TCR 库的多阶段异质性。我们报告了一种鉴定 GC 患者预后生物标志物的新方法，并加深了我们对胃癌变过程中免疫反应的理解。
