Affiliation:
1. Geneseq Biosciences , Melbourne, Victoria , Australia
2. Australian Clinical Laboratories , Clayton, Victoria , Australia
3. The University of Melbourne , Parkville, Victoria , Australia
4. Newcastle Skin Check , New South Wales , Australia
5. School of Medicine, University of Queensland , Queensland , Australia
Abstract
Abstract
Background
Noninvasive molecular biomarkers are needed to improve the early, accurate and precise diagnosis of invasive cutaneous melanoma.
Objectives
To independently validate a previously identified circulating microRNA signature of melanoma (MEL38), and, secondly, to develop a complementary microRNA signature, optimized for prognostication.
Patients and Methods
MicroRNA expression profiling was performed on plasma samples from a multicentre observational case–control study, involving patients with primary or metastatic melanoma, melanoma in situ, nonmelanoma skin cancer, or benign naevi. MicroRNA profiles from patients with length of survival, treatment and sentinel lymph node biopsy (SLNB) data were used to develop the prognostic signature. The primary outcome of interest for MEL38 was its association with melanoma status, including area under the curve, binary diagnostic sensitivity and specificity, and incidence-adjusted positive and negative predictive values. The prognostic signature was assessed using rates of survival per risk group and relationship to conventional predictors of outcome.
Results
Circulating microRNA profiles of 372 patients with invasive melanoma and 210 control individuals were generated. The average age of all participants was 59 years; 49% were male. A MEL38 score > 5.5 indicated the presence of invasive melanoma. Overall, 551/582 (95%) of patients were correctly diagnosed, with 93% sensitivity and 98% specificity. MEL38 score ranged from 0 to 10 with an area under the curve of 0.98 (95% confidence interval 0.97–0.99, P < 0.001). A novel prognostic 12-microRNA signature (MEL12) developed from 232 patients identified low-, standard- or high-risk groups, with 94%, 78% and 58% rates of 10-year melanoma-specific survival, respectively (log-rank P < 0.001). MEL12 prognostic risk groups were significantly associated with clinical staging (χ2, P < 0.001) and SLNB status (P = 0.027). Patients who were classified as high risk by MEL12 were approximately three times more likely to have melanoma detected in their sentinel lymph nodes compared to low-risk patients.
Conclusions
The circulating MEL38 signature may assist in diagnosing patients with invasive melanoma vs. other conditions associated with a lower – or negligible – risk of mortality. A complementary and prognostic MEL12 signature is predictive of SLNB status, clinical stage and probability of survival. Plasma microRNA profiling may help to optimize existing diagnostic pathways as well as enable personalized, risk-informed melanoma treatment decisions.
Publisher
Oxford University Press (OUP)
Cited by
1 articles.
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