Sun Guoping, Qiu Lumei, Cheng Zhiqiang, Pan Weibing, Qiu Jingjun, Zou Chang, Xie Ni, Liu Song, Zhu Peng, Zeng Jun, Dai Yong
Core Laboratory, Pingshan New District People's Hospital, Shenzhen, Guangdong 518118, P.R. China.
Clinical Medical Research Center, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China.
Oncol Lett. 2018 Aug;16(2):1584-1592. doi: 10.3892/ol.2018.8800. Epub 2018 May 24.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Complementarity-determining region 3 (CDR3) of B-cell receptors (BCRs) and T-cell receptors are the major site of antigen recognition, which determines a unique clone type, and are considered to be the representative of the disease. In the present study, high-throughput sequencing was used to analyze the association of characteristics of the BCR immunoglobulin heavy chain (IGH) and the T-cell receptor β chain (TRB) CDR3 genes in PTC and corresponding pericarcinous tissues from patients. A difference of CDR3 length distributions of total IGH CDR3 sequences between the two groups was revealed. IGHV3-11/IGHJ6, TRBV2/TRBJ1-2 and TRBV2/TRBJ1-1 may be biomarkers for the development of PTC. Furthermore, it was revealed that the extent of the common clonotype expressions at the amino acid level was slightly higher compared with the nucleotide level. The Shannon entropy demonstrated a diversity reduction in PTC compared with the pericarcinous group, and the highly expended clone (HEC) expression of PTC was higher compared with that of the corresponding pericarcinous group. Additionally, the highest clone frequency percentage of IGH and TRB was at 0.1-1.0% degree of expansion, as HEC expression was higher in PTC compared with the matched group. There was no shared clone of HECs in the two groups either at the amino acid level or at the nucleotide expression level. The differential expression of CDR3 sequences of PTC have been identified in the present study. Further research is required for assessing the immune repertoire size, diversity, cloning tracking and finding public clones of T-cell and B-cell populations in the development of PTC.
甲状腺乳头状癌(PTC)是最常见的甲状腺癌类型。B细胞受体(BCR)和T细胞受体的互补决定区3(CDR3)是抗原识别的主要部位,决定了独特的克隆类型,被认为是该疾病的代表。在本研究中,采用高通量测序分析PTC患者及其相应癌旁组织中BCR免疫球蛋白重链(IGH)和T细胞受体β链(TRB)CDR3基因特征的相关性。揭示了两组之间总IGH CDR3序列的CDR3长度分布存在差异。IGHV3-11/IGHJ6、TRBV2/TRBJ1-2和TRBV2/TRBJ1-1可能是PTC发生发展的生物标志物。此外,研究发现氨基酸水平上常见克隆型表达的程度略高于核苷酸水平。香农熵显示PTC组与癌旁组织相比多样性降低,PTC组的高扩增克隆(HEC)表达高于相应癌旁组织。此外,IGH和TRB的最高克隆频率百分比在0.1-1.0%的扩增程度,因为PTC组的HEC表达高于匹配组。两组在氨基酸水平或核苷酸表达水平上均不存在HEC的共享克隆。本研究已鉴定出PTC中CDR3序列的差异表达。在PTC发生发展过程中,评估T细胞和B细胞群体的免疫组库大小、多样性、克隆追踪以及寻找公共克隆,还需要进一步研究。