Survival Distinctions for Cases Representing Immunologically Cold Tumors via Intrinsic Disorder Assessments for Blood-Sourced TRB Variable Regions

• Published in: International journal of molecular sciences Vol. 25; no. 21; p. 11691
• Main Authors: Sahoo, Arpan, Gozlan, Etienne C, Song, Joanna J, Angelakakis, George, Yeagley, Michelle, Chobrutskiy, Boris I, Huda, Taha I, Blanck, George
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01-11-2024; MDPI
• Subjects: Antigens; Cancer; Chemotherapy; Cold; Genetic aspects; Genomics; Lymphocytes; Melanoma; Metastasis; Neuroblastoma; Statistical significance; T cell receptors; T cells; Tumors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms252111691

T cell receptor beta (TRB) sequences were recovered from the Cancer Genome Atlas Uveal Melanoma blood exome files. Intrinsic disorder scores for amino acid (AA) sequences of the entire TRB variable region were obtained and evaluated as potentially representative of overall survival (OS) distinctions, i.e., for cases representing the upper and lower 50th percentiles for intrinsic disorder scores. Analyses using four intrinsic disorder assessment tools indicated that a lower intrinsic disorder of the blood-sourced TRB variable regions, including continuous AA sequences of the V-gene segment, the complementarity-determining region-3, and the J-gene segment, was associated with a better OS probability (with log-rank p-values ranging from 0.002 to 0.014). We further determined that intrinsic disorder assessments could be used for OS stratification for a second, immunologically cold cancer: MYCN amplified neuroblastoma. Thus, intrinsic disorder assessments of blood-sourced, full TRB variable regions may provide a novel patient stratification approach for patients with immunologically cold cancers.