PLA1A expression as a diagnostic marker of BRAF-mutant metastasis in melanoma cancer

Abstract

BRAF and NRAS are the most reported mutations associated to melanomagenesis. The lack of accurate diagnostic markers in response to therapeutic treatment in BRAF/NRAS-driven melanomagenesis is one of the main challenges in melanoma personalized therapy. In order to assess the diagnostic value of phosphatidylserine-specific phospholipase A1-alpha (PLA1A), a potent lysophospholipid mediating the production of lysophosphatidylserine, PLA1A mRNA and serum levels were compared in subjects with malignant melanoma (n = 18), primary melanoma (n = 13), and healthy subjects (n = 10). Additionally, the correlation between histopathological subtypes of BRAF/NRAS-mutated melanoma and PLA1A was analyzed. PLA1A expression was significantly increased during melanogenesis and positively correlated to disease severity and histopathological markers of metastatic melanoma. PLA1A mRNA and serum levels were significantly higher in patients with BRAF-mutated melanoma compared to the patients with NRAS-mutated melanoma. Notably, PLA1A can be used as a diagnostic marker for an efficient discrimination between naïve melanoma samples and advanced melanoma samples (sensitivity 91%, specificity 57%, and AUC 0.99), as well as BRAF-mutated melanoma samples (sensitivity 62%, specificity 61%, and AUC 0.75). Our findings suggest that PLA1A can be considered as a potential diagnostic marker for advanced and BRAF-mutated melanoma.