Abstract
BackgroundIdentification of melanoma patients at high risk for recurrence and monitoring for recurrence are critical for informed management decisions. We hypothesized that serum microRNAs (miRNAs) could provide prognostic information at the time of diagnosis unaccounted for by the current staging system and could be useful in detecting recurrence after resection.MethodsWe screened 355 miRNAs in sera from 80 melanoma patients at primary diagnosis (discovery cohort) using a unique quantitative reverse transcription-PCR (qRT-PCR) panel. Cox proportional hazard models and Kaplan-Meier recurrence-free survival (RFS) curves were used to identify a miRNA signature with prognostic potential adjusting for stage. We then tested the miRNA signature in an independent cohort of 50 primary melanoma patients (validation cohort). Logistic regression analysis was performed to determine if the miRNA signature can determine risk of recurrence in both cohorts. Selected miRNAs were measured longitudinally in subsets of patients pre-/post-operatively and pre-/post-recurrence.ResultsA signature of 5 miRNAs successfully classified melanoma patients into high and low recurrence risk groups with significant separation of RFS in both discovery and validation cohorts (p = 0.0036, p = 0.0093, respectively). Significant separation of RFS was maintained when a logistic model containing the same signature set was used to predict recurrence risk in both discovery and validation cohorts (p < 0.0001, p = 0.033, respectively). Longitudinal expression of 4 miRNAs in a subset of patients was dynamic, suggesting miRNAs can be associated with tumor burden.ConclusionOur data demonstrate that serum miRNAs can improve accuracy in identifying primary melanoma patients with high recurrence risk and in monitoring melanoma tumor burden over time.
Highlights
Identification of melanoma patients at high risk for recurrence and monitoring for recurrence are critical for informed management decisions
The evolving paradigm shift towards a molecular characterization of melanoma to improve prognostic accuracy, detect recurrence, and better guide management decisions has largely been devoid of blood-based miRNA studies
We show that serum-based miRNAs demonstrate hallmarks of useful tumor markers, namely easy detection in accessible samples and promising clinical utility and applicability in melanoma
Summary
Identification of melanoma patients at high risk for recurrence and monitoring for recurrence are critical for informed management decisions. Despite the benefit of early detection of locoregional and distant metastases amenable to curative resection [3,5], there is no consensus on either the selection or timing of imaging studies and laboratory tests for use in followup [6]. This is in part due to the limited sensitivity and specificity of available imaging modalities and blood tests, coupled with considerable economic cost [7]
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