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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.
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1 The Affiliated Hospital of Southwest Medical University, Department of Oncology, Luzhou, China (GRID:grid.488387.8); Anyue Hospital of Traditional Chinese Medicine, Second Ziyang Hospital of Traditional Chinese Medicine, Department of Oncology, Ziyang, China (GRID:grid.488387.8)
2 The Affiliated Hospital of Southwest Medical University, Department of Oncology, Luzhou, China (GRID:grid.488387.8)
3 University of Tehran, Laboratory of Systems Biology and Bioinformatics, Institute of Biochemistry and Biophysics, Tehran, Iran (GRID:grid.46072.37) (ISNI:0000 0004 0612 7950); Tehran Medical Sciences, Islamic Azad University, Department of Genetics, Faculty of Advanced Science and Technology, Tehran, Iran (GRID:grid.411463.5) (ISNI:0000 0001 0706 2472)
4 University of Zanjan, Department of Biology, Faculty of Science, Zanjan, Iran (GRID:grid.412673.5) (ISNI:0000 0004 0382 4160)
5 Southwest Medical University, Department of Pharmacology, School of Pharmacy, Luzhou, China (GRID:grid.410578.f) (ISNI:0000 0001 1114 4286); China Medical University, Graduate Institute of Biomedical Sciences, Research Center for Cancer Biology, and Center for Molecular Medicine, Taichung, Taiwan (GRID:grid.254145.3) (ISNI:0000 0001 0083 6092)
6 The Affiliated Hospital of Southwest Medical University, Department of Pathology, Luzhou, China (GRID:grid.488387.8)
7 Army Medical University (Third Military Medical University), Institute of Materia Medical, College of Pharmacy, Chongqing, China (GRID:grid.410570.7) (ISNI:0000 0004 1760 6682)
8 Tehran Medical Sciences, Islamic Azad University, Department of Genetics, Faculty of Advanced Science and Technology, Tehran, Iran (GRID:grid.411463.5) (ISNI:0000 0001 0706 2472)