A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer.

A Plasma Biomarker Panel of Four MicroRNAs for the Diagnosis of Prostate Cancer.
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DOI:
10.1038/s41598-018-24424-w
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发表时间:
2018-04-27
期刊:
影响因子:
4.6
通讯作者:
Batra J
Batra J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Matin F;Jeet V;Moya L;Selth LA;Chambers S;Australian Prostate Cancer BioResource;Clements JA;Batra J

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全球每年有超过100万男性被诊断为前列腺癌,但目前的诊断模式不足以识别重大癌症,更可靠的早期诊断生物标志物对于改善前列腺癌患者的临床管理是必要的。微小RNA(miRNAs)调节促成癌症的重要细胞过程/途径,并且稳定地存在于体液中。在这项研究中,我们分析了年龄匹配的前列腺癌患者和健康对照者在治疗开始前(约60%的患者)和治疗开始后/治疗期间(约40%的患者)收集的血浆中的372种癌症相关miRNA,并观察到4种miRNA- miR-4289、miR-326、miR-152- 3 p和miR-98- 5 p的水平升高,这在一个独立的队列中得到了验证。miRNA组能够区分前列腺癌患者和对照组(AUC = 0.88)。对来自临床样本的已发表的miRNA转录组学数据的分析表明,与邻近的非恶性组织相比,miR-152- 3 p在肿瘤中的表达较低。miR-152- 3 p的过表达增加了前列腺癌细胞的增殖和迁移,表明该miRNA在前列腺癌发病机制中的作用,这一概念得到了预测的miR-152- 3 p靶基因的途径分析的支持。总之,包括miR-152- 3 p在内的四种miRNA组可能靶向在前列腺癌发病机制中起关键作用的基因,具有改善早期前列腺癌诊断的潜力。
Prostate cancer is diagnosed in over 1 million men every year globally, yet current diagnostic modalities are inadequate for identification of significant cancer and more reliable early diagnostic biomarkers are necessary for improved clinical management of prostate cancer patients. MicroRNAs (miRNAs) modulate important cellular processes/pathways contributing to cancer and are stably present in body fluids. In this study we profiled 372 cancer-associated miRNAs in plasma collected before (~60% patients) and after/during commencement of treatment (~40% patients), from age-matched prostate cancer patients and healthy controls, and observed elevated levels of 4 miRNAs - miR-4289, miR-326, miR-152-3p and miR-98-5p, which were validated in an independent cohort. The miRNA panel was able to differentiate between prostate cancer patients and controls (AUC = 0.88). Analysis of published miRNA transcriptomic data from clinical samples demonstrated low expression of miR-152-3p in tumour compared to adjacent non-malignant tissues. Overexpression of miR-152-3p increased proliferation and migration of prostate cancer cells, suggesting a role for this miRNA in prostate cancer pathogenesis, a concept that was supported by pathway analysis of predicted miR-152-3p target genes. In summary, a four miRNA panel, including miR-152-3p which likely targets genes with key roles in prostate cancer pathogenesis, has the potential to improve early prostate cancer diagnosis.
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