Plasma lncRNA expression profile as a prognostic tool in BRAF-mutant metastatic melanoma patients treated with BRAF inhibitor
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Tomasz Kolenda1,2, Piotr Rutkowski4, Michał Michalak5, Katarzyna Kozak4, Kacper Guglas1,2,3, Marcel Ryś1, Łukasz Galus6,7, Sebastian Woźniak6, Iwona Ługowska4,8, Aleksandra Gos9, Anna Teresiak2, Andrzej Mackiewicz1,10, Katarzyna Lamperska2 and Jacek Mackiewicz6,10,11
1 Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, Poznan, Poland
2 Laboratory of Cancer Genetics, Greater Poland Cancer Centre, Poznan, Poland
3 Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland
4 Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland
5 Department of Computer Science and Statistics, University of Medical Sciences, Poznan, Poland
6 Department of Medical and Experimental Oncology, Heliodor Swiecicki Clinical Hospital, Poznan University of Medical Sciences, Poznan, Poland
7 Department of Chemotherapy, Greater Poland Cancer Centre, Poznan, Poland
8 Early Phase Clinical Trials Unit, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland
9 Department of Translational Oncology, Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland
10 Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, Poznan, Poland
11 Department of Biology and Environmental Sciences, Poznan University of Medical Sciences, Poznan, Poland
Keywords: melanoma; BRAF mutation; BRAF inhibitor; lncRNA; liquid biopsy
Received: December 06, 2018 Accepted: May 13, 2019 Published: June 11, 2019
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.
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