Prognostic insights in skin melanoma: A study of differential diagnostic tissue markers.

Abstract

e21576 Background: Cutaneous melanoma is the most aggressive form of skin cancer, necessitating reliable prognostic markers for risk stratification. Despite the availability of clinical parameters such as Breslow thickness and ulceration, accurate molecular prognostic markers remain a major unmet need. Molecular tools like DecisionDx-Melanoma (31 genes) and MelaGenix (11 genes) provide advanced risk classification for recurrence and survival. Previously, we identified novel RNA markers distinguishing melanomas from nevi (NCT04353050), distinct from those commonly investigated for prognostication. These markers include melanoma-specific CXCL8, DUXAP8/9/10, MAGEA3/6/12, and nevus-specific circCDR1-AS (LINC00632) and CMIP. This study evaluates whether these markers serve as reliable prognostic indicators in melanoma patients. Methods: Formalin-fixed, paraffin-embedded (FFPE) melanoma samples from 120 patients (59 with good prognosis, 61 with poor prognosis) were analyzed. Good prognosis was defined as event-free survival of ≥10 years, while poor prognosis was defined as recurrence, metastasis, or death within ≤5 years. A previously validated RT-PCR panel was employed to assess correlations between marker expression and prognosis. Results: Of 120 melanoma samples, informative results were obtained for 119 using standard procedures. Among the 120 samples, 80 showed definitive melanoma-specific markers, 27 fell into a "grey zone," and 13 exhibited no conclusive melanoma markers. Expression levels of melanoma-specific markers correlated with Breslow thickness but not prognosis. We performed a subgroup analysis stratified into thick (≥4 mm) and thin (≤1 mm) melanomas (Table). The strong prognostic value of CXCL8 and DUXAP8_9_10 in thick melanomas suggests their involvement in aggressive tumor behavior, potentially linked to inflammatory and proliferative pathways. CMIP expression inversely correlated with poor prognosis, indicating its possible role in less aggressive melanoma subtypes. In contrast, no markers demonstrated significant prognostic utility in thin melanomas, highlighting the need for alternative molecular signatures. Conclusions: These findings suggest that RNA marker panels could enhance current prognostic models for thick melanomas. However, their utility in thin melanomas remains limited, warranting further investigation into alternative molecular signatures. Future studies should focus on identifying additional biomarkers to improve risk stratification in early-stage melanoma patients. Marker AUROC P value RNA-markers prognostic significance in thick (≥4 mm) melanomas  CXCL8 0.65 0.004  CMIP 0.37 0.011  DUXAP8_9_10 0.61 0.032  cirCDR1.AS 0.41 0.083  MAGEA3_6 0.54 0.470 RNA-markers prognostic significance in thin (≤1 mm) melanomas  DUXAP8_9_10 0.32 0.021  MAGEA3_6 0.35 0.056  cirCDR1.AS 0.59 0.285  CXCL8 0.59 0.318  CMIP 0.48 0.838