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首页> 美国卫生研究院文献>Oncotarget >Plasma lncRNA expression profile as a prognostic tool in BRAF-mutant metastatic melanoma patients treated with BRAF inhibitor
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Plasma lncRNA expression profile as a prognostic tool in BRAF-mutant metastatic melanoma patients treated with BRAF inhibitor

机译：血浆lncRNA表达谱作为BRAF抑制剂治疗的BRAF突变型转移性黑色素瘤患者的预后工具

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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.
机译：长的非编码RNA（lncRNA）在许多癌症类型中均失调。这些lncRNA的异常基线水平在癌症患者中显示出诊断和预后的潜力。这项研究的目的是评估血浆lncRNA在使用BRAF抑制剂治疗的BRAF突变晚期黑色素瘤患者中的预后价值。从58例晚期BRAF突变型黑素瘤患者和15例健康供体收集的血浆样品中分离出总RNA。使用LncProfiler qPCR阵列试剂盒（SBI）和LightCycler 96（Roche）评估了90个lncRNA的表达水平。 LncRNA表达水平与对BRAF抑制剂（vemurafenib）治疗的反应相关。根据患者的lncRNA水平将其分为具有不同lncRNA表达（低，中和高）的三类。使用Cox比例风险回归模型确定接受vemurafenib的患者与无进展生存期和总生存期（分别为PFS和OS）显着相关的lncRNA。与健康供体相比，黑色素瘤患者中的12个lncRNA的表达水平下调，而五个lncRNA的表达上调。 Kaplan-Meier分析表明，11种和16种不同的lncRNA的上调或下调分别与更长的中位PFS和OS相关。进一步的分析表明，IGF2AS，抗Peg11，MEG3，Zeb2NAT的基线lncRNAs是接受vemurafenib治疗的BRAF突变晚期黑色素瘤患者的独立预后因素。评估血浆lncRNAs表达水平用于晚期黑色素瘤的诊断和预后评估似乎是一种安全而有价值的方法。但是，这种方法需要在更大的队列和随机试验中进一步验证。

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