Abstract
Purpose
A very large and still expanding collection of adaptive immune receptor (IR) recombination reads, representing many diseases, is becoming available for downstream analyses. Among the most productive approaches has been to establish risk stratification parameters via the chemical features of the IR complementarity determining region-3 (CDR3) amino acid (AA) sequences, particularly for large datasets where clinical information is available. Because the IR CDR3 AA sequences often play a large role in antigen binding, the chemistry of these AAs has the likelihood of representing a disease-related fingerprint as well as providing pre-screening information for candidate antigens. To approach this issue in a novel manner, we developed a bladder cancer, case evaluation approach based on CDR3 aromaticity.
Methods
We developed and applied a simple and efficient algorithm for assessing aromatic, chemical complementarity between T-cell receptor (TCR) CDR3 AA sequences and the cancer specimen mutanome.
Results
Results indicated a survival distinction for aromatic CDR3-aromatic mutanome complementary, versus non-complementary, bladder cancer case sets. This result applied to both tumor resident and blood TCR CDR3 AA sequences and was supported by CDR3 AA sequences represented by both exome and RNAseq files.
Conclusion
The described aromaticity factor algorithm has the potential of assisting in prognostic assessments and guiding immunotherapies for bladder cancer.
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Abbreviations
- AA:
-
Amino acid
- BCG:
-
Bacillus Calmette–Guerin
- BLCA:
-
Bladder cancer
- CDR3:
-
Complementarity determining region-3
- CS:
-
(Chemical) complementarity score
- dbGaP:
-
Database of genotypes and phenotypes
- GDC:
-
Genomic data commons
- IR:
-
Immune receptor
- LUSC:
-
Lung squamous carcinoma
- KM:
-
Kaplan–Meier
- NA:
-
Not available
- OS:
-
Overall survival
- SKCM:
-
Skin cutaneous melanoma
- TCGA:
-
The cancer genome atlas
- TCR:
-
T-cell receptor
- TRA:
-
T-cell receptor alpha
- TRB:
-
T-cell receptor beta
- WXS:
-
Whole exome sequence
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Acknowledgements
Authors thank USF research computing and Ms. Corinne Walters, for administrative assistance with the NIH approval process for dataset access. Authors thank the taxpayers of the State of Florida.
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JWW: conceptualization; data curation; investigation; formal analysis; writing—early drafts; writing—review and editing. KWM: conceptualization; methodology: software. VRB: formal analysis; methodology: software. ECG: methodology; software. MY: methodology; software. GB: conceptualization; methodology; project administration; resources; supervision; writing—review and editing. FWM: conceptualization; methodology; project administration; resources; supervision; writing—review and editing.
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Waweru, J.W., Mwangi, K.W., Barker, V.R. et al. Delineation of a T-cell receptor CDR3-cancer mutanome aromaticity factor, assessable via blood samples, that facilitates the establishment of survival distinctions in bladder cancer. J Cancer Res Clin Oncol 149, 4359–4366 (2023). https://doi.org/10.1007/s00432-022-04339-w
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DOI: https://doi.org/10.1007/s00432-022-04339-w