Determination of the complexity and diversity of the TCR β‑chain CDR3 repertoire in bladder cancer using high‑throughput sequencing

Ma,Jingsheng; Sun,Guoping; Zhu,Peng; Liu,Song; Ou,Minglin; Chen,Zhiqiang; Zou,Chang; Chan,Frank Leing; Dai,Yong; Sui,Weiguo

doi:10.3892/ol.2019.10015

Determination of the complexity and diversity of the TCR β‑chain CDR3 repertoire in bladder cancer using high‑throughput sequencing

Authors:
- Jingsheng Ma
- Guoping Sun
- Peng Zhu
- Song Liu
- Minglin Ou
- Zhiqiang Chen
- Chang Zou
- Frank Leing Chan
- Yong Dai
- Weiguo Sui
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Affiliations: Nephrology Department, Guangxi Key Laboratory of Metabolic Diseases Research, Guilin No. 181 Hospital (The Affiliated Guilim Hospital of Southern Medical University), Guilin, Guangxi 541002, P.R. China, Central Laboratory of Shenzhen Pingshan People's Hospital, Shenzhen, Guangdong 518118, P.R. China, Clinical Medical Research Center of The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, Guangdong 518020, P.R. China, Cancer Biology and Experimental Therapeutics, School of Biomedical Sciences, The Chinese University of Hong Kong, SAR, P.R. China
Published online on: February 5, 2019 https://doi.org/10.3892/ol.2019.10015
Pages: 3808-3816
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the complexity and diversity of the T lymphocyte immune repertoire in patients with bladder cancer. To do so, the immune state of patients was assessed. The study also aimed to elucidate the aetiology and pathogenesis of bladder cancer to provide a novel theoretical basis for disease prevention, diagnosis, treatment and prognosis monitoring. Cancerous and paracancerous (control) tissue samples were collected from five patients diagnosed with muscle‑invasive bladder cancer. Multiplex polymerase chain reaction and Illumina high‑throughput sequencing were used to determine the characteristics and clonal diversity of the T‑cell receptor (TCR) β‑chain complementarity‑determining region 3 (CDR3) gene in the cancerous and paracancerous tissues of patients with bladder cancer. The degree of clonal expansion in malignant samples was significantly higher than in adjacent samples. Furthermore, ΤCRβ variable (TRBV), ΤCRβ diversity (TRBD) and ΤCRβ joining (TRBJ) repertoires were significantly different in cancerous samples compared with adjacent samples. In addition, 13 identified V‑J pairs were highly expressed in cancerous samples whereas they had low expression in control samples. In conclusion, the degree of T‑cell clonal expansion in bladder cancerous tissue was higher than in paracancerous tissue, whereas the immune diversity of the tissues of patients with bladder cancer was significantly lower. The DNA sequence and amino acid sequences, and V‑J combination level may be used to comprehensively understand the diversity and characteristics of TCR CDR3 in bladder cancer and paracancerous tissues, and to evaluate the immune status of bladder cancer to develop therapeutic targets and biomarkers for prognosis monitoring.

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