What question did this study set out to answer?

To validate the MEL12 microRNA signature as a prognostic biomarker for early-stage melanoma in tissue samples across profiling platforms.

March 16, 2026Open Access

Validation of a Prognostic microRNA Signature in Early-Stage Melanoma Across NanoString and RNA-Sequencing Platforms

RLRyan K. van LaarAgriBio LCLauren CoombsAgriBio CLChristopher G. LoveAgriBio

Key Points

To validate the MEL12 microRNA signature as a prognostic biomarker for early-stage melanoma in tissue samples across profiling platforms.
Conducted a retrospective analysis of 277 stage I-II melanoma patients with survival data.
Stratified participants into training and independent validation cohorts.
Performed microRNA expression profiling using NanoString and RNA-sequencing platforms.
Developed a principal component-based Cox regression model using cross-validation techniques.
In the training cohort, the MEL12 score showed a C-index of 0.82 for melanoma-specific survival (MSS).
Validation confirmed a C-index of 0.77 for MSS and 0.63 for overall survival (OS).
High-risk patients exhibited significantly worse 15-year MSS in both cohorts.
The MEL12 score remained independently associated with MSS after adjusting for clinicopathologic variables.
No significant interaction was found between MEL12 score and measurement platform.

Abstract

Background: Most patients with early-stage invasive melanoma have excellent outcomes, yet a minority experience disease progression and melanoma-specific death.Identifying these high-risk patients at diagnosis remains a significant clinical challenge.We previously validated the MEL12 microRNA signature as a prognostic biomarker in plasma samples.Here, we evaluate whether this signature retains its prognostic value when measured in formalin-fixed paraffin-embedded (FFPE) tumour tissue and assess its performance across two microRNA expression profiling platforms. Methods:We conducted a retrospective analysis of 277 stage I-II melanoma patients with up to 15-year survival data, stratified into training (n=179) and independent validation (n=98) cohorts.MicroRNA expression profiling was performed using both NanoString and RNA-sequencing platforms.A principal component-based Cox regression model was developed using leave-one-out cross-validation in the training cohort, with frozen model parameters applied to the validation cohort.The primary endpoint was melanoma-specific survival (MSS), with overall survival (OS) as secondary endpoint.Results: In the training cohort, the MEL12 score showed strong prognostic performance for MSS (C-index=0.82,HR=5.32 per SD, p<0.001) and OS (C-index=0.73,HR=2.90 per SD, p<0.001).These findings were confirmed in independent validation for both MSS (C-index=0.77,HR=3.34, p=0.002) and OS (C-index=0.63,HR=1.28, p=0.17).High-risk patients experienced significantly worse 15-year MSS in both cohorts (training HR=9.61, p<0.001; validation HR=8.40, p<0.001).In multivariable analysis adjusting for clinicopathologic variables, the MEL12 score remained independently associated with MSS and platform analysis revealed no significant interaction between MEL12 score and measurement platform. Conclusions:The MEL12 microRNA signature represents a potentially valuable prognostic biomarker for identifying early-stage melanoma patients at high risk of poor outcomes, maintaining consistent performance when measured in FFPE tissue across different expression profiling platforms.These results support further investigation into integrating genomic risk stratification with traditional histopathologic assessment.

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