Plasma microRNA profiles: identification of miR-744 as a novel diagnostic and prognostic biomarker in pancreatic cancer.
Plasma microRNA profiles: identification of miR-744 as a novel diagnostic and prognostic biomarker in pancreatic cancer.
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DOI：
10.1038/bjc.2015.366
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发表时间：
2015-11-17
影响因子：
8.8
通讯作者：
Otsuji E
中科院分区：
文献类型：
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作者：
Miyamae M;Komatsu S;Ichikawa D;Kawaguchi T;Hirajima S;Okajima W;Ohashi T;Imamura T;Konishi H;Shiozaki A;Morimura R;Ikoma H;Ochiai T;Okamoto K;Taniguchi H;Otsuji E
本研究旨在探索血浆中新的microRNA，用于使用基于microRNA阵列的方法筛查胰腺癌（PCa）患者的癌症并预测临床结局。我们使用Toray 3D-Gene microRNA阵列方法比较PCa患者和健康志愿者之间的血浆水平。(1)选择在血浆中具有高表达的六种致癌microRNA（miR-615- 5 p、-744、-575、-557、-675和-550a）。(2)通过使用来自94名PCa患者和68名健康志愿者的血浆样本的定量RT-PCR，在小规模分析（P=0.0038）、两个独立队列分析和大规模分析（P<0.0001，AUC 0.8307）中验证了PCa患者的血浆miR-744水平显著高于健康志愿者。(3)miR-744在PCa组织（P=0.0069）和PCa细胞系（P=0.0074）中的表达分别显著高于正常组织和成纤维细胞。术前血浆miR-744水平在术后样本中显著降低（P=0.0063）。(4)血浆中高水平的miR-744是胰腺癌患者胰腺切除术后独立的不良预后因素（P = 0.0007，HR 21.2（3.17-436）），与淋巴结转移（P= 0.0407）和复发（P=0.0376）相关。此外，高水平的血浆miR-744导致接受基于吉西他滨的化疗的不可手术的PCa患者的无进展生存率较差（P=0.0533）。miR-744在PCa细胞中的过表达在体外诱导了对吉西他滨的显著化学抗性。血浆miR-744可能是筛查PCa、监测和预测PCa患者不良预后及化疗耐药的有用生物标志物。
This study aims to explore novel microRNAs in plasma for screening cancer and predicting clinical outcomes in pancreatic cancer (PCa) patients using a microRNA array-based approach. We used the Toray 3D-Gene microRNA array-based approach to compare plasma levels between PCa patients and healthy volunteers. (1) Six oncogenic microRNAs (miR-615-5p, -744, -575, -557, -675, and -550a) with high expression in plasma were selected. (2) By quantitative RT–PCR using plasma samples from 94 PCa patients and 68 healthy volunteers, a significantly higher level of plasma miR-744 in PCa patients than in healthy volunteers was validated in small-scale analysis (P=0.0038), two independent cohort analyses, and large-scale analysis (P<0.0001, AUC 0.8307). (3) miR-744 expression was significantly higher in PCa tissues (P=0.0069) and PCa cell lines (P=0.0074) than in normal tissues and fibroblasts, respectively. Preoperative plasma level of miR-744 was significantly reduced in postoperative samples (P=0.0063). (4) A high level of plasma miR-744, which was correlated with lymph node metastasis (P=0.0407) and recurrences (P=0.0376), was an independent poor prognostic factor of PCa patients after pancreatectomy (P=0.0007, HR 21.2 (3.17–436)). Furthermore, a high level of plasma miR-744 contributed to poorer progression-free survival of non-operable PCa patients who underwent gemcitabine-based chemotherapy (P=0.0533). Overexpression of miR-744 in PCa cells induced significant chemoresistance to gemcitabine in vitro. Plasma miR-744 might be useful biomarker for screening PCa, monitoring, and predicting poor prognosis and chemoresistance in PCa patients.