Wang Fengyan, Deng Li, Li Ziqiang, Cao Qiwei, Jiang Runze, Xu Changqing, Yang Jing
Department of Gastroenterology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, China.
Shandong Provincial Key Laboratory of Neuroprotective Drugs, Zibo, China.
Technol Cancer Res Treat. 2025 Jan-Dec;24:15330338251329699. doi: 10.1177/15330338251329699. Epub 2025 Mar 28.
PurposeHepatocellular carcinoma (HCC) is the most common liver malignancy in the world, and tumor-infiltrating T cells have been shown to be closely related to the prognosis of HCC. This study investigated the potential and efficacy of T cell receptor (TCR) repertoire characterization as a biomarker for predicting survival differences.MethodsIn this study, we used high-throughput sequencing technology to systematically analyze the characteristics of TCR repertoires in tumor tissues obtained from 23 long-survivors and 8 short-survivors diagnosed with HCC.ResultsThe TCR composition in HCC long-survivors was found to be less diverse than in the short-survivors. In addition, in the context of V and J gene segments, long-survivors showed significantly higher usage of TRBJ1-3, TRBV10-1, TRBV15, and TRBV6-5, and lower usage of TRBJ2-2. Both principal component analysis (PCA) and the motif diagram of complementary determination region 3 (CDR3) sequences could clearly discriminate short- and long-survivors. And there were five up-regulated and one down-regulated CDR3 sequences in the LS group compared with the SS group. According to the characteristics of TCR repertoire, we also established the survival-related evaluation system and the prediction model for the survival period of HCC patients.ConclusionOur study adds to the existing knowledge of TCR rearrangement profiles in HCC patients by elucidating the differential TCR rearrangement profiles between long-term and short-term surviving HCC patients. Also, our analysis identified a number of TCR genes that are significantly associated with survival, and these may not only serve as prognostic biomarkers but may also play an important role in antigen-specific immunotherapy.
目的
肝细胞癌（HCC）是全球最常见的肝脏恶性肿瘤，肿瘤浸润性T细胞已被证明与HCC的预后密切相关。本研究调查了T细胞受体（TCR）库特征作为预测生存差异生物标志物的潜力和功效。
方法
在本研究中，我们使用高通量测序技术系统分析了从23例长期存活者和8例短期存活者的HCC肿瘤组织中获得的TCR库特征。
结果
发现HCC长期存活者的TCR组成比短期存活者的多样性更低。此外，在V和J基因片段方面，长期存活者显示TRBJ1-3、TRBV10-1、TRBV15和TRBV6-5的使用频率显著更高，而TRBJ2-2的使用频率更低。主成分分析（PCA）和互补决定区3（CDR3）序列的基序图都能清楚地区分短期和长期存活者。与短期存活组相比，长期存活组有5个CDR3序列上调和1个下调。根据TCR库的特征，我们还建立了HCC患者生存相关评估系统和生存期预测模型。
结论
我们的研究通过阐明长期和短期存活的HCC患者之间TCR重排谱的差异，增加了对HCC患者TCR重排谱的现有认识。此外，我们的分析确定了一些与生存显著相关的TCR基因，这些基因不仅可作为预后生物标志物，还可能在抗原特异性免疫治疗中发挥重要作用。
