Abstract
With lung cancer remaining a challenging disease, new approaches to biomarker discovery and therapy development are needed. Recent immunogenomics, adaptive immune receptor approaches have indicated that it is very likely that B cells play an important role in mediating better overall outcomes. As such, we assessed physicochemical features of lung adenocarcinoma resident IGL complementarity determining region-3 (CDR3) amino acid (AA) sequences and determined that hydrophobic CDR3 AA sequences were associated with a better disease-free survival (DFS) probability. Further, using a recently developed chemical complementarity scoring algorithm particularly suitable for the evaluation of large patient datasets, we determined that IGL CDR3 chemical complementarity with certain cancer testis antigens was associated with better DFS. Chemical complementarity scores for IGL CDR3-MAGEC1 represented a gender bias, with an overrepresentation of males among the higher IGL-CDR3-CTA complementarity scores that were in turn associated with better DFS (logrank p < 0.065). Overall, this study pointed towards potential biomarkers for prognoses that, in some cases are likely gender-specific; and towards biomarkers for guiding therapy, e.g., IGL-based opportunities for antigen targeting in the lung cancer setting.
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Provided in the SOM.
Abbreviations
- AA:
-
Amino acid
- BCR:
-
B-cell receptor
- CDR3:
-
Complementarity determining region-3
- CS:
-
Complementarity score
- EAGLE:
-
Environment and genetics in lung cancer etiology
- Hydro CS:
-
(Uversky) Hydropathy-based complementarity score
- IR:
-
(Adaptive) Immune receptor
- LUAD:
-
Lung adenocarcinoma
- RSEM:
-
RNAseq, expectation–maximization
- SKCM:
-
Skin cutaneous melanoma
- TCGA:
-
The cancer genome atlas
- TCR:
-
T-cell receptor
- TME:
-
Tumor microenvironment
- WXS:
-
Whole exome sequence
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Acknowledgements
Authors acknowledge the extensive support of USF research computing; the administrative support of Ms. Corinne Walters in managing the dataset approval process; and the taxpayers of the State of Florida. Dedicated to Dana.
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SVC: conceptualization; formal analysis; methodology; visualization; writing—review & editing. TIH: formal analyses; methodology; software. DNP: formal analysis; methodology; software. MY: formal analysis; methodology; software. JFA: methodology; software. KJC: formal analysis; methodology. ECG: methodology; software. AC: Resources; methodology; software. BIC: methodology; software. GB: conceptualization; formal analysis; methodology; Software; visualization; writing—review & editing.
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Access to the TCGA-LUAD and TCGA-SKCM exome files was via National Institutes of Health (NIH), database of genotypes and phenotypes (dbGaP) project approval number 6300 for George Blanck. Access to the RNAseq files was via NIH, dbGaP project approval number 20312 for George Blanck.
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Charkowick, S.V., Huda, T.I., Patel, D.N. et al. IGL CDR3 Hydropathy and Antigen Chemical Complementarity Associated with Greater Disease-Free Survival in Lung Adenocarcinoma: Implications for Gender Disparities. Biochem Genet 62, 530–546 (2024). https://doi.org/10.1007/s10528-023-10437-2
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DOI: https://doi.org/10.1007/s10528-023-10437-2