Liu Xicheng, Cui Yuanyuan, Zhang Yaoxian, Liu Zhanli, Zhang Qiuli, Wu Wenyan, Zheng Zihao, Li Shien, Zhang Zhongjun, Li Yali
Department of Anesthesiology, Shenzhen People's Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen, Guangdong, China.
Mol Genet Genomic Med. 2019 Mar;7(3):e504. doi: 10.1002/mgg3.504. Epub 2019 Jan 9.
Colorectal cancer (CRC) is the 3rd most common cancer type in the world. The correlation between immune repertoire and prognosis of CRC has been well studied in the last decades. The diversity and stability of the immune cells can be measured by hypervariable complementarity-determining region 3 (CDR3) segments of the T-cell receptor (TCR).
In this study, we collected five healthy controls and 19 CRC patients' peripheral blood mononuclear cells (PBMCs) in three stages, namely 1 day preoperative, 3 days' postoperative, and 7 days' postoperative, respectively. Simultaneously, we have also done the comparative analysis of these two different anesthesia methods, namely TIVA and CEGA. Sequencing of the TCR segments has been performed by multiplex PCR and high-throughput next-generation sequencing. We also analyzed the distribution of CDR3 length, highly expansion clones (HECs), TRBV, and TRBJ gene usage.
Our result showed a significant difference between TCR CDR3 length distribution and HEC distribution between CRC patients and healthy controls. We also found that TRBV11-2, TRBV12-1, TRBV16, TRBV3-2, TRBV4-2, TRBV4-3, TRBV5-4, TRBV6-8, TRBV7-8, TRBV7-9 and RBV11-2, TRBV12-1, TRBV16, TRBV3-2, TRBV4-2, TRBV4-3, TRBV5-4, TRBV6-8, TRBV7-8, and TRBV7-9 usages are different between CRC patients and healthy controls.
In conclusion, CRC patients were presented with different immune repertoire in comparison with healthy controls. In this study, significant difference in TRBV and TRBJ gene usage in between case and control group could provide some potential biomarker for the diagnosis and the treatment of the patients with CRC.
结直肠癌(CRC)是全球第三大常见癌症类型。在过去几十年中,免疫库与CRC预后之间的相关性已得到充分研究。免疫细胞的多样性和稳定性可以通过T细胞受体(TCR)的高变互补决定区3(CDR3)片段来衡量。
在本研究中,我们分别收集了5名健康对照者和19名CRC患者在术前1天、术后3天和术后7天三个阶段的外周血单个核细胞(PBMC)。同时,我们还对全凭静脉麻醉(TIVA)和静吸复合麻醉(CEGA)这两种不同的麻醉方法进行了对比分析。通过多重PCR和高通量下一代测序对TCR片段进行测序。我们还分析了CDR3长度分布、高度扩增克隆(HEC)、TRBV和TRBJ基因使用情况。
我们的结果显示,CRC患者与健康对照者之间TCR CDR3长度分布和HEC分布存在显著差异。我们还发现,CRC患者与健康对照者在TRBV11-2、TRBV12-1、TRBV16、TRBV3-2、TRBV4-2、TRBV4-3、TRBV5-4、TRBV6-8、TRBV7-8、TRBV7-9以及RBV11-2、TRBV12-1、TRBV16、TRBV3-2、TRBV4-2、TRBV4-3、TRBV5-4、TRBV6-8、TRBV7-8和TRBV7-9的使用情况上存在差异。
总之,与健康对照者相比,CRC患者表现出不同的免疫库。在本研究中,病例组和对照组之间TRBV和TRBJ基因使用的显著差异可为CRC患者的诊断和治疗提供一些潜在的生物标志物。