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

Abstract

This corrects the article DOI: 10.1038/bjc.2017.85.

Figure 1

Training and independent validation series results. (A) Training series support vector machine (SVM): MEL38 scores generated from circulating microRNA profiles of normal control individuals and melanoma patients with stage I–IV disease. (B) A 28-gene subset of MEL38 applied to circulating microRNA profiles generated from blood collected from normal controls and melanoma patients with stage I–IV disease (n=57). The 28-gene subset SVM was partially retrained with leave-one-out cross validation to and applied to the peripheral blood microRNA independent validation series. 3C Independent validation of the microRNA signature of melanoma in. (C) Solid line: ROC analysis of the SVM classifier as trained on the 48-sample Nanostring discovery series. AUC=0.79, P<0.001. Dotted line: ROC analysis of the SVM classifier partially retrained on the 57 sample independent validation series using the 28 out of 38 genes available. AUC=0.94, P<0.001.

Figure 2

Additional independent validation series. (A) Hierarchical clustering of microRNA expression levels in melanoma cell line A375, normal melanocyte cell line and exosomes experimentally isolated from both cell lines shows separation between disease status phenotypes. (B) MEL38 SVM score calculated from microRNA expression data from normal skin and melanoma cell lines, and their respective exosomes isolated from tissue culture. (C) Hierarchical clustering of MEL38 measured in melanoma and nevus FFPE tissue, profiled using Agilent microRNA microarrays. Clear separation based on disease status can be seen, supporting the hypothesis that genes in the MEL38 signature originate from melanoma or nevi cells. (D) MEL38 SVM scores calculated on microRNA gene expression profiles generated from FFPE nevi and melanoma biopsies. Case IDs are shown on x axis, MEL38 SVM classification score on Y axis. SVM=support vector machine.

Figure 3

Circulating microRNA and melanoma clinical stage. (A) Venn diagram of MEL38 (diagnostic) and MEL18 (staging) signatures. (B) Line plot of MEL18 gene expression fold-changes relative to melanoma stage I. Each gene in MEL18 exhibits significant difference between one or more stages of melanoma progress and has a correlation coefficient of +0.7 or −0.7 with stage I–IV disease.