Long non-coding RNAs (lncRNA) are dysregulated in many cancer types. Abnormal baseline levels of these lncRNAs display diagnostic and prognostic potential in cancer patients. The aim of this study was to evaluate the prognostic value of plasma lncRNAs in BRAF -mutant advanced melanoma patients treated with a BRAF inhibitor. Total RNA was isolated from plasma samples collected from 58 advanced BRAF-mutant melanoma patients and 15 healthy donors. The expression levels of 90 lncRNAs were estimated using the LncProfiler qPCR Array Kit (SBI) and LightCycler 96 (Roche). LncRNA expression levels correlated with responses to the BRAF inhibitor (vemurafenib) treatment. The patients were stratified into three groups based on their lncRNA levels with various lncRNA expressions (low, medium, and high). A Cox proportional hazards regression model was used to determine the lncRNAs that were significantly associated with both progression-free and overall survivals (PFS and OS, respectively) in patients receiving vemurafenib. The expression level of 12 lncRNAs was down-regulated, while five lncRNAs were up-regulated in melanoma patients compared to healthy donors. Kaplan-Meier analysis showed that upregulation or downregulation of 11 and 16 different lncRNAs were associated with longer median PFS and OS, respectively. Further analysis demonstrated that the baseline lncRNAs for IGF2AS, anti-Peg11, MEG3, Zeb2NAT are independent prognostic factors in BRAF -mutant advanced melanoma patients treated with vemurafenib. Evaluation of plasma lncRNAs expression level for advanced melanoma diagnosis and prognosis evaluation appears to be a safe and valuable method; however, this method requires further validation in larger cohorts and randomized trials.
Background: Uveal melanoma (UM) is the most common intraocular tumour in adults with a poor prognosis and extremely high mortality rate due to the development of metastatic disease. However, despite relatively good knowledge about the histological and genetic risk factors for metastasis development, there is no specific biomarker that would allow early detection of UM progression. Recently, exosomes and their molecular cargo have been widely studied in the search for potential biomarkers in several cancers. The purpose of this study was to analyze the inflammation-related protein cargo of exosomes derived from the serum of primary and metastatic UM patients and healthy donors. Methods: The exosomes were isolated from the serum of primary and metastatic UM patients and healthy donors. Using multiplex immunoassay technology, we analyzed the concentration of 37 inflammation-related proteins in obtained exosomes. Results: The analysis of protein cargo showed several molecules related to inflammation, such as interferon-gamma, interleukin 2, 22 and 12(p40), Pentraxin-3, TNFSF13B and TNFSF8 which were significantly enriched in metastatic UM exosomes. We showed a significant correlation between the disease stage and the concentration of these inflammation-related proteins from exosomal cargo. Conclusions: Based on the obtained results, we propose the panel of exosomal proteins for early detection of uveal melanoma progression into metastatic disease.
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