Hu antigen R (HuR) heterogeneous expression quantification as a prognostic marker of melanoma

Abstract

Background

Prognostic markers for melanoma, particularly for stage II disease, are needed for the risk benefit evaluation of future adjuvant therapies. The mainly nuclear RNA-binding protein HuR regulates the protein expression of thousands of mRNAs, its own heterogeneous expression could therefore reflect tumor heterogeneity and plasticity. Here, we evaluate its quantification in primary melanoma as a marker of metastatic outcome.

Methods

We conducted an immunohistochemistry-based automated quantification of HuR nuclear expression heterogeneity in primary melanomas most with Breslow thickness ≥ 1 mm and calculated the dimensionless fourth moment, i.e. the Kurtosis of HuR (HuR K) expression distribution. 12 tumors from patients with no metastatic disease were compared to a similar number of tumors from patients who had metastatic disease at two years follow-up.

Results

HuR K value, appeared significantly higher in the non-metastatic group comparatively to the metastatic group (P=2.84 × 10⁻³, one-tail Wilcoxon rank-sum test). Moreover, compared to the Breslow thickness, HuR K value appeared as a more robust marker of metastatic outcome (respective areas under ROC curves 0.84 and 0.87).

Conclusion

Our data need confirmation on a large cohort, however strongly suggest that HuR expression heterogeneity quantification using kurtosis, could be used as a prognostic marker in melanoma.