Stage-specific prognostic biomarkers in melanoma.

Yabin Cheng,Guohong Zhang,Anand Rotte,Youwen Zhou,Xuezhu Xu,Gholamreza Safaee Ardekani,Jing Lu,Guangdi Chen,Magdalena Martinka,Kevin J Mcelwee

doi:10.18632/oncotarget.2907

Abstract

The melanoma staging system proposed by the American Joint Committee on Cancer (AJCC) (which classifies melanoma patients into four clinical stages) is currently the most widely used tool for melanoma prognostication, and clinical management decision making by clinicians. However, multiple studies have shown that melanomas within specific AJCC Stages can exhibit varying progression and clinical outcomes. Thus, additional information, such as that provided by biomarkers is needed to assist in identifying the patients at risk of disease progression. Having previously found six independent prognostic biomarkers in melanoma, including BRAF, MMP2, p27, Dicer, Fbw7 and Tip60, our group has gone on to investigate if these markers are useful in risk stratification of melanoma patients in individual AJCC stages. First, we performed Kaplan-Meier survival and Cox proportional multivariate analyses comparing prognostication power of these markers in 254 melanoma patients for whom the expression levels were known, identifying the best performing markers as candidates for stage-specific melanoma markers. We then verified the results by incorporating an additional independent cohort (87 patients) and in a combined cohort (341 patients). Our data indicate that BRAF and MMP2 are optimal prognostic biomarkers for AJCC Stages I and II, respectively (P = 0.010, 0.000, Log-rank test); whereas p27 emerged as a good marker for AJCC Stages III/IV (0.018, 0.046, respectively, log-rank test). Thus, our study has identified stage-specific biomarkers in melanoma, a finding which may assist clinicians in designing improved personalized therapeutic modalities.

Highlights

Melanoma is one of the most notorious human cancers with high mortality, due to its aggressiveness and resistance to traditional chemo- and radio- therapies
Using the same set of melanoma tissue microarrays, we found that BRAF expression and MMP2 expression are the best markers for American Joint Committee on Cancer (AJCC) Stages I and II, respectively, whereas p27 cytoplasm expression is a superior prognostic marker for patients in both Stages III and IV
The prognosis of each of the AJCC Stages in both the discovery cohort (Supplementary Figure S1a) and in the combined confirmation cohort (Supplementary Figure S1b) is similar and consistent with that reported in studies with larger samples from other laboratories, suggesting that our study patient populations are representative [3, 4]

Summary

Introduction

Melanoma is one of the most notorious human cancers with high mortality, due to its aggressiveness and resistance to traditional chemo- and radio- therapies. This disease arises from abnormal melanocyte proliferation, and can occur in any anatomic location containing melanocytes [1]. The American Joint Committee on Cancer (AJCC) melanoma staging system is currently www.impactjournals.com/oncotarget widely used for melanoma classification, prognostic prediction, and individualized therapy design. This system classifies individual patients into four stages: Stage I and Stage II define primary invasive melanomas, whereas Stage III and Stage IV define local regional and distant metastases, respectively [3]

Methods

Results

Conclusion