MicroRNA profiling in canine multicentric lymphoma
MicroRNA profiling in canine multicentric lymphoma
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DOI：
10.1371/journal.pone.0226357
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发表时间：
2019-12-11
期刊：
影响因子：
3.7
通讯作者：
Wood, R. Darren
中科院分区：
文献类型：
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作者：
Craig, Karlee K. L.;Wood, Geoffrey A.;Wood, R. Darren
淋巴瘤是狗最常见的造血系统肿瘤，与人类疾病非常相似。肿瘤生物标志物的发现为诊断和预测治疗反应和临床结果提供了新工具。 MicroRNA 是参与转录后基因调控的小型非编码 RNA，其异常表达可能会影响与癌症相关的基因。本研究的目的是比较患有多中心 B 或 T 细胞淋巴瘤的狗与健康对照狗的淋巴结和血浆中 microRNA 的表达特征。我们进一步比较了淋巴结和相应血浆样本之间的表达，并评估了复发时与诊断时相比表达的变化。最后，我们研究了 microRNA 与接受 CHOP 化疗的患者临床结果的关系。使用定制的 PCR 阵列来分析 38 种犬类目标 microRNA。使用实时 RT-qPCR 进行定量，并通过 delta-delta Ct 方法确定相对表达。在淋巴结中，B 细胞淋巴瘤有 16 个 microRNA 表达显着改变，T 细胞淋巴瘤有 9 个 microRNA 表达显着改变。在血浆中，有 15 个针对 B 细胞淋巴瘤的 microRNA 发生改变，3 个针对 T 细胞淋巴瘤发生改变。大多数microRNA在淋巴结和血浆之间没有相关表达，只有8个microRNA在诊断和复发之间存在显着差异。对于 B 细胞淋巴瘤，与完全缓解时完成 CHOP 的狗相比，非缓解组中有 8 个 microRNA 有差异表达。其中四种 microRNA 在一年前死亡的患者中也发生了改变。高与低 microRNA 表达的 Kaplan-Meier 生存曲线显示，10 个 microRNA 与无进展生存期相关，3 个与总生存期相关。这项研究重点介绍了对犬多中心淋巴瘤感兴趣的 microRNA。未来的目标包括开发可用作生物标志物的 microRNA 组合，旨在为兽医癌症患者提供改进的结果预测。
Lymphoma is the most common hematopoietic tumour in dogs and is remarkably similar to the human disease. Tumour biomarker discovery is providing new tools for diagnostics and predicting therapeutic response and clinical outcome. MicroRNAs are small non-coding RNAs that participate in post-transcriptional gene regulation and their aberrant expression can impact genes involved in cancer. The aim of this study was to characterize microRNA expression in lymph nodes and plasma from dogs with multicentric B or T cell lymphoma compared to healthy control dogs. We further compared expression between lymph nodes and corresponding plasma samples and assessed changes in expression at relapse compared to time of diagnosis. Lastly, we investigated microRNAs for association with clinical outcome in patients treated with CHOP chemotherapy. A customized PCR array was utilized to profile 38 canine target microRNAs. Quantification was performed using real time RT-qPCR and relative expression was determined by the delta-delta Ct method. In lymph nodes, there were 16 microRNAs with significantly altered expression for B cell lymphoma and 9 for T cell lymphoma. In plasma, there were 15 microRNAs altered for B cell lymphoma and 3 for T cell lymphoma. The majority of microRNAs did not have correlated expression between lymph node and plasma and only 8 microRNAs were significantly different between diagnosis and relapse. For B cell lymphoma, 8 microRNAs had differential expression in the non-remission group compared to dogs that completed CHOP in complete remission. Four of these microRNAs were also altered in patients that died prior to one-year. Kaplan-Meier survival curves for high versus low microRNA expression revealed that 10 microRNAs were correlated with progression-free survival and 3 with overall survival. This study highlights microRNAs of interest for canine multicentric lymphoma. Future goals include development of microRNA panels that may be useful as biomarkers with the intent to provide improved outcome prediction to veterinary cancer patients.