C-Met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition
C-Met/miR-130b axis as novel mechanism and biomarker for castration resistance state acquisition
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DOI：
10.1038/onc.2016.505
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发表时间：
2017-06-29
期刊：
影响因子：
8
通讯作者：
Bonci, D.
中科院分区：
文献类型：
--
作者：
Cannistraci, A.;Federici, G.;Bonci, D.
尽管前列腺癌的一个重要子集在整个生命中都处于惰性状态，但晚期前列腺癌仍然是癌症相关死亡的主要原因之一。没有可靠的标志来区分懒惰和好斗的形式。在这里，我们强调了一种新的分子电路，涉及microRNA和编码促进癌症进展和去势抵抗的基因。我们的临床前和临床数据表明，c-Met激活增加miR-130b水平，抑制雄激素受体的表达，促进肿瘤扩散和抵抗激素消融治疗。这些发现的相关性在患者样本上和在Taylor‘s平台的独立患者队列的计算机分析中得到了证实。数据表明，c-Met/miR-130b轴可作为患者风险评估的新的预后标记物和治疗抵抗的指标。我们的结果为病理的所有阶段的治疗决策提出了新的生物标志物。数据可能有助于确定需要接受辅助治疗的高危患者，以及耐阉割形式的替代疗法，同时有助于确定可能的抗Met治疗患者。此外，我们还证明了从手术候选人和晚期患者的外周血中分离的外体中Met/miR-130b轴的表达是可能的，为主动监测和治疗监测提供了一种新的非侵入性工具。
Although a significant subset of prostate tumors remain indolent during the entire life, the advanced forms are still one of the leading cause of cancer-related death. There are not reliable markers distinguishing indolent from aggressive forms. Here we highlighted a new molecular circuitry involving microRNA and coding genes promoting cancer progression and castration resistance. Our preclinical and clinical data demonstrated that c-Met activation increases miR-130b levels, inhibits androgen receptor expression, promotes cancer spreading and resistance to hormone ablation therapy. The relevance of these findings was confirmed on patients' samples and by in silico analysis on an independent patient cohort from Taylor's platform. Data suggest c-Met/miR-130b axis as a new prognostic marker for patients' risk assessment and as an indicator of therapy resistance. Our results propose new biomarkers for therapy decision-making in all phases of the pathology. Data may help identify high-risk patients to be treated with adjuvant therapy together with alternative cure for castration-resistant forms while facilitating the identification of possible patients candidates for anti-Met therapy. In addition, we demonstrated that it is possible to evaluate Met/miR-130b axis expression in exosomes isolated from peripheral blood of surgery candidates and advanced patients offering a new non-invasive tool for active surveillance and therapy monitoring.