Tumour-educated platelets for breast cancer detection: biological and technical insights

Background Studies have shown that blood platelets contain tumour-specific mRNA profiles tumour-educated platelets (TEPs). Here, we aim to train a TEP-based breast cancer detection classifier. Methods Platelet mRNA was sequenced from 266 women with stage I–IV breast cancer and 212 female controls fr...

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Bibliographic Details
Published in:British journal of cancer 2023-04, Vol.128 (8), p.1572-1581
Main Authors: Liefaard, Marte C., Moore, Kat S., Mulder, Lennart, van den Broek, Daan, Wesseling, Jelle, Sonke, Gabe S., Wessels, Lodewyk F. A., Rookus, Matti, Lips, Esther H.
Format: Article
Language:English
Subjects:
631/114/1305
631/337/2019
692/4028/67/1347
692/4028/67/1857
692/53/2421
Biomedical and Life Sciences
Biomedicine
Blood Platelets
Breast cancer
Breast Neoplasms - diagnosis
Breast Neoplasms - genetics
Cancer Research
Drug Resistance
Epidemiology
Female
Gene expression
Hospitals
Humans
Molecular Medicine
Oncology
Platelets
Population studies
Reproducibility of Results
Support Vector Machine
Support vector machines
Tumors
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Summary:Background Studies have shown that blood platelets contain tumour-specific mRNA profiles tumour-educated platelets (TEPs). Here, we aim to train a TEP-based breast cancer detection classifier. Methods Platelet mRNA was sequenced from 266 women with stage I–IV breast cancer and 212 female controls from 6 hospitals. A particle swarm optimised support vector machine (PSO-SVM) and an elastic net-based classifier (EN) were trained on 71% of the study population. Classifier performance was evaluated in the remainder (29%) of the population, followed by validation in an independent set (37 cases and 36 controls). Potential confounding was assessed in post hoc analyses. Results Both classifiers reached an area under the curve (AUC) of 0.85 upon internal validation. Reproducibility in the independent validation set was poor with an AUC of 0.55 and 0.54 for the PSO-SVM and EN classifier, respectively. Post hoc analyses indicated that 19% of the variance in gene expression was associated with hospital. Genes related to platelet activity were differentially expressed between hospitals. Conclusions We could not validate two TEP-based breast cancer classifiers in an independent validation cohort. The TEP protocol is sensitive to within-protocol variation and revision might be necessary before TEPs can be reconsidered for breast cancer detection.
ISSN:0007-0920
1532-1827
DOI:10.1038/s41416-023-02174-5