TY - JOUR
T1 - Multicentre analysis of nucleic acid quantification using aqueous humour liquid biopsy in uveal melanoma
T2 - implications for clinical testing
AU - Pike, Sarah B.
AU - Reid, Mark W.
AU - Peng, Chen Ching
AU - Chang, Christina
AU - Xu, Benjamin Y.
AU - Gombos, Dan S.
AU - Patel, Sapna
AU - Xu, Liya
AU - Berry, Jesse L.
N1 - Publisher Copyright:
© 2023 Canadian Ophthalmological Society
PY - 2023
Y1 - 2023
N2 - Objective: Uveal melanoma (UM) tumour biopsy is limited by size and intratumour heterogeneity. We explored the potential of aqueous humour (AH) liquid biopsy for UM by quantifying analytes in samples collected at diagnosis and after brachytherapy to look for clinical correlations with tumour features. Design: Case-series study. Participants: Sixty-six UM patients and 16 control subjects from a tertiary care hospital. Methods: The study included 119 UM AH samples and 16 control samples analyzed for unprocessed analytes (i.e., dsDNA, miRNA, and protein) using Qubit fluorescence assays. Results: Analytes were widely quantifiable among available UM AH samples (dsDNA: 94.1%; miRNA: 88.0%; protein: 95.2%) at significantly higher concentrations than among control samples (dsDNA, p = 0.008; miRNA, p < 0.0001; protein, p = 0.007). In samples taken at diagnosis, concentrations were higher at more advanced American Joint Cancer Commission stages; when comparing most advanced stage III with least advanced stage I, median dsDNA was 4 times greater (p < 0.0001), miRNA was 2 times greater (p = 0.001), and protein was 3 times greater (p < 0.0001). Analytes were quantifiable in >70% of diagnostic samples from eyes with tumours <2 mm tall. Height had a positive association with diagnostic analyte concentrations (dsDNA: R = 0.43, p = 0.0007; miRNA: R = 0.35, p = 0.01; protein: R = 0.39, p = 0.005). Samples taken after brachytherapy showed significantly higher concentrations than diagnostic samples (p < 0.01 for all). Conclusions: UM AH is a rich repository of analytes. Samples from eyes with more advanced stage and larger tumours had higher concentrations, though analytes also were quantifiable in eyes with smaller, less advanced tumours. Future analysis of AH analytes may be informative in the pursuit of personalized UM treatments.
AB - Objective: Uveal melanoma (UM) tumour biopsy is limited by size and intratumour heterogeneity. We explored the potential of aqueous humour (AH) liquid biopsy for UM by quantifying analytes in samples collected at diagnosis and after brachytherapy to look for clinical correlations with tumour features. Design: Case-series study. Participants: Sixty-six UM patients and 16 control subjects from a tertiary care hospital. Methods: The study included 119 UM AH samples and 16 control samples analyzed for unprocessed analytes (i.e., dsDNA, miRNA, and protein) using Qubit fluorescence assays. Results: Analytes were widely quantifiable among available UM AH samples (dsDNA: 94.1%; miRNA: 88.0%; protein: 95.2%) at significantly higher concentrations than among control samples (dsDNA, p = 0.008; miRNA, p < 0.0001; protein, p = 0.007). In samples taken at diagnosis, concentrations were higher at more advanced American Joint Cancer Commission stages; when comparing most advanced stage III with least advanced stage I, median dsDNA was 4 times greater (p < 0.0001), miRNA was 2 times greater (p = 0.001), and protein was 3 times greater (p < 0.0001). Analytes were quantifiable in >70% of diagnostic samples from eyes with tumours <2 mm tall. Height had a positive association with diagnostic analyte concentrations (dsDNA: R = 0.43, p = 0.0007; miRNA: R = 0.35, p = 0.01; protein: R = 0.39, p = 0.005). Samples taken after brachytherapy showed significantly higher concentrations than diagnostic samples (p < 0.01 for all). Conclusions: UM AH is a rich repository of analytes. Samples from eyes with more advanced stage and larger tumours had higher concentrations, though analytes also were quantifiable in eyes with smaller, less advanced tumours. Future analysis of AH analytes may be informative in the pursuit of personalized UM treatments.
UR - http://www.scopus.com/inward/record.url?scp=85179812688&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85179812688&partnerID=8YFLogxK
U2 - 10.1016/j.jcjo.2023.10.024
DO - 10.1016/j.jcjo.2023.10.024
M3 - Article
C2 - 38036045
AN - SCOPUS:85179812688
SN - 0008-4182
JO - Canadian Journal of Ophthalmology
JF - Canadian Journal of Ophthalmology
ER -