Characterization of T-Cell Receptor Profiles Predicts Survival Situation in Patients with Hepatocellular Carcinoma.

Abstract

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.