A high range of intrinsic disorder values for tumor resident, T-cell receptor beta V-complementarity determining region 3-J amino acid sequence assemblies correlates with better melanoma outcomes.
Joyce J Zhu, Arpan Sahoo, Joanna J Song, Veda Naga Priya Vangala, Utsav Kapoor, George Blanck
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引用次数: 0
Abstract
Metastatic melanoma is characterized by high rates of treatment resistance. While various factors have been studied for their prognostic significance, this study evaluated the potential prognostic value of the intrinsic disorder of T-cell receptor beta (TRB) polypeptides. TRB recombination sequencing reads were extracted from tumor RNA-seq files representing The Cancer Genome Atlas, Skin Cutaneous Melanoma dataset, and genomics files representing the National Institutes of Health, phs002683 dataset. Intrinsic disorder values were computed for the TRB V-complementarity determining region 3 (CDR3)-J amino acid sequences for all cases. Survival analyses assessed overall survival and disease-specific survival for case sets based on assigning cases to upper or lower 50th percentile groups, based in turn on intrinsic disorder values. For the phs002683 dataset, intrinsic disorder values were compared between cases representing resistance to immune checkpoint inhibitors (ICIs) and cases representing no observed resistance. The results indicated that the upper 50th percentile of the range of intrinsic disorder values was linked to better outcomes. This was obtained for two TRB datasets representing different RNA-seq file, recombination read extraction algorithms, and was observed for two different intrinsic disorder models. Furthermore, low minimum various long-3 and various short-long 2 values correlated with ICI treatment resistance. The findings of this study suggest that the diversity of intrinsic disorder values representing TRB V-CDR3-J assemblies may represent a novel prognostic biomarker for metastatic melanoma cases and a potential biomarker for indicating different personalized treatments.
期刊介绍:
Melanoma Research is a well established international forum for the dissemination of new findings relating to melanoma. The aim of the Journal is to promote the level of informational exchange between those engaged in the field. Melanoma Research aims to encourage an informed and balanced view of experimental and clinical research and extend and stimulate communication and exchange of knowledge between investigators with differing areas of expertise. This will foster the development of translational research. The reporting of new clinical results and the effect and toxicity of new therapeutic agents and immunotherapy will be given emphasis by rapid publication of Short Communications. Thus, Melanoma Research seeks to present a coherent and up-to-date account of all aspects of investigations pertinent to melanoma. Consequently the scope of the Journal is broad, embracing the entire range of studies from fundamental and applied research in such subject areas as genetics, molecular biology, biochemistry, cell biology, photobiology, pathology, immunology, and advances in clinical oncology influencing the prevention, diagnosis and treatment of melanoma.