Molecular Diagnostics | Published:

Development and validation of a plasma-based melanoma biomarker suitable for clinical use

British Journal of Cancer volume 118, pages 857866 (20 March 2018) | Download Citation

This article has been updated

Abstract

Background:

In Australia, more money is spent on skin cancer than any other malignancy. Despite this, the mortality rate of melanoma, the deadliest form, has steadily increased over the past 50 years. Diagnostic imprecision and a lack of complimentary molecular biomarkers are partially responsible for this lack of progress.

Methods:

Whole-microRNAome profiling was performed on plasma samples from 32 patients with histologically confirmed melanoma and 16 normal controls. A classification algorithm was trained on these data and independently validated on multiple previously published microRNA data sets, representing (i) melanoma patient- and normal-blood, (ii) melanoma and nevi biopsy tissue, and (iii) cell lines and purified exosomes.

Results:

38 circulating microRNAs had biologically and statistically significant differences between melanoma and normal plasma samples (MEL38). A support vector machine algorithm, trained on these markers, showed strong independent classification accuracy (AUC 0.79–0.94). A majority of MEL38 genes have been previously associated with melanoma and are known regulators of angiogenesis, metastasis, tumour suppression, and treatment resistance.

Conclusions:

MEL38 exhibits disease state specificity and robustness to platform and specimen-type variation. It has potential to become an objective diagnostic biomarker and improve the precision and accuracy of melanoma detection and monitoring.

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Change history

  • 20 March 2018

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Acknowledgements

We acknowledge the physicians, patients, and control individuals who contributed to this study and to K Eisenbud and A Zielinska for helpful discussions and manuscript editing assistance.

Author information

Affiliations

  1. Geneseq Biosciences Pty Ltd, PO Box 309, Balaclava, VIC 3183, Victoria, Australia

    • Ryan Van Laar
    • , Mitchel Lincoln
    •  & Barton Van Laar

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Competing interests

Geneseq Biosciences is a privately-held start-up company, aiming to develop a novel diagnostic biomarker for melanoma detection and management. A provisional patent application has been filed on the work described herein and we are actively pursuing clinical and technical validation partners locally and nationally.

Corresponding author

Correspondence to Ryan Van Laar.

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DOI

https://doi.org/10.1038/bjc.2017.477

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Supplementary Information accompanies this paper on British Journal of Cancer website (http://www.nature.com/bjc)