Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients.
Novel, non-invasive markers for detecting therapy induced neuroendocrine differentiation in castration-resistant prostate cancer patients.
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DOI：
10.1038/s41598-021-87441-2
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发表时间：
2021-04-15
影响因子：
4.6
通讯作者：
Saini S
中科院分区：
文献类型：
--
作者：
Bhagirath D;Liston M;Akoto T;Lui B;Bensing BA;Sharma A;Saini S
神经内分泌前列腺癌(NEPC)是去势耐受前列腺癌(CRPC)的一种高度侵袭性变种，通常通过神经内分泌分化和雄激素途径抑制剂的治疗而出现。目前，NEPC的诊断具有挑战性，因为现有的标志物还不够特异。我们的目标是识别新的、基于细胞外小泡(EV)的生物标记物来诊断NEPC。为此，我们对从具有腺癌特征的CRPC患者(CRPC-ADANO)和CRPC-NE的队列中分离的血清EV进行了小RNA下一代测序，发现182个已知的和4个新的miRNAs存在显著的调控异常。我们利用机器学习算法开发了一个‘EV-miRNA分类器’，它可以很好地将‘CRPC-NE’与‘CRPC-Adeno’区分开来。对NEPC细胞模型外切体的蛋白质谱进行了质谱分析，确定凝血酶原蛋白1(TSP1)是一种特异的生物标志物。鉴于我们的结果，我们建议miRNA面板和TSP1可以作为新的、非侵入性的工具来识别NEPC并指导治疗决策。总之，我们的研究首次确定了新的基于非侵入性胞外/胞外囊泡的生物标记物，用于检测晚期去势抵抗前列腺癌患者的神经内分泌分化，这对目前极具挑战性的这些患者的临床管理具有重要的翻译意义。
Neuroendocrine prostate cancer (NEPC), a highly aggressive variant of castration-resistant prostate cancer (CRPC), often emerges upon treatment with androgen pathway inhibitors, via neuroendocrine differentiation. Currently, NEPC diagnosis is challenging as available markers are not sufficiently specific. Our objective was to identify novel, extracellular vesicles (EV)-based biomarkers for diagnosing NEPC. Towards this, we performed small RNA next generation sequencing in serum EVs isolated from a cohort of CRPC patients with adenocarcinoma characteristics (CRPC-Adeno) vs CRPC-NE and identified significant dysregulation of 182 known and 4 novel miRNAs. We employed machine learning algorithms to develop an ‘EV-miRNA classifier’ that could robustly stratify ‘CRPC-NE’ from ‘CRPC-Adeno’. Examination of protein repertoire of exosomes from NEPC cellular models by mass spectrometry identified thrombospondin 1 (TSP1) as a specific biomarker. In view of our results, we propose that a miRNA panel and TSP1 can be used as novel, non-invasive tools to identify NEPC and guide treatment decisions. In conclusion, our study identifies for the first time, novel non-invasive exosomal/extracellular vesicle based biomarkers for detecting neuroendocrine differentiation in advanced castration resistant prostate cancer patients with important translational implications in clinical management of these patients that is currently extremely challenging.
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影响因子：
82.9
作者：
Beltran H;Prandi D;Mosquera JM;Benelli M;Puca L;Cyrta J;Marotz C;Giannopoulou E;Chakravarthi BV;Varambally S;Tomlins SA;Nanus DM;Tagawa ST;Van Allen EM;Elemento O;Sboner A;Garraway LA;Rubin MA;Demichelis F
通讯作者：
Demichelis F
影响因子：
4.8
作者：
Fujita, Yasunori;Kojima, Keitaro;Ito, Masafumi
通讯作者：
Ito, Masafumi
醋酸阿比特龙对初治转移性去势抵抗性前列腺癌神经内分泌分化的影响
影响因子：
2.8
作者：
Dong, Baijun;Fan, Liancheng;Xue, Wei
通讯作者：
Xue, Wei
DOI：
10.1007/978-1-4939-3347-1_13
发表时间：
2016-01-01
期刊：
CANCER DRUG RESISTANCE: OVERVIEWS AND METHODS
影响因子：
--
作者：
Andre, Maria do Rosario;Pedro, Ana;Lyden, David
通讯作者：
Lyden, David
影响因子：
11.2
作者：
Bhagirath D;Yang TL;Bucay N;Sekhon K;Majid S;Shahryari V;Dahiya R;Tanaka Y;Saini S
通讯作者：
Saini S