肿瘤驻留的高范围内在紊乱值,t细胞受体β v -互补决定区域3-J氨基酸序列组装与更好的黑色素瘤预后相关。

IF 1.9 4区 医学 Q3 DERMATOLOGY
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

摘要

转移性黑色素瘤的特点是治疗耐药率高。虽然各种因素的预后意义已被研究,但本研究评估了t细胞受体β (TRB)多肽内在紊乱的潜在预后价值。TRB重组测序读数是从代表癌症基因组图谱的肿瘤RNA-seq文件中提取的,皮肤皮肤黑色素瘤数据集,以及代表美国国立卫生研究院的基因组文件,phs002683数据集。计算了所有病例TRB v -互补决定区3 (CDR3)-J氨基酸序列的内在无序值。生存分析评估病例组的总生存期和疾病特异性生存期,基于将病例分配到上或下50百分位组,依次基于内在紊乱值。对于phs002683数据集,比较了代表免疫检查点抑制剂(ICIs)耐药的病例和代表未观察到耐药的病例之间的内在紊乱值。结果表明,内在障碍值范围的前50百分位数与更好的结果有关。这是对代表不同RNA-seq文件的两个TRB数据集,重组读取提取算法,以及两种不同的内在无序模型的观察结果。不同长-3最小值和不同短-长- 2最小值与抗ICI处理相关。本研究结果表明,代表TRB V-CDR3-J组件的内在紊乱值的多样性可能代表转移性黑色素瘤病例的新的预后生物标志物,以及指示不同个性化治疗的潜在生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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.

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.

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来源期刊
Melanoma Research
Melanoma Research 医学-皮肤病学
CiteScore
3.40
自引率
4.50%
发文量
139
审稿时长
6-12 weeks
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.
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