Circulating microRNA-203 predicts prognosis and metastasis in human colorectal cancer.
Circulating microRNA-203 predicts prognosis and metastasis in human colorectal cancer.
复制标题
DOI：
10.1136/gutjnl-2014-308737
复制
发表时间：
2017-04
期刊：
影响因子：
24.5
通讯作者：
Goel A
中科院分区：
文献类型：
--
作者：
Hur K;Toiyama Y;Okugawa Y;Ide S;Imaoka H;Boland CR;Goel A
远处转移是CRC患者死亡的主要原因，部分原因是缺乏可靠的转移预测生物标志物。尽管miR-203在癌症转移中具有重要功能，但其在CRC转移中的临床意义仍然未知。在这里，我们评估了血清miR-203作为CRC转移的非侵入性生物标志物的潜在作用。通过qRT-PCR定量58对原发性CRC（pCRC）和相应的匹配肝转移（LM）以及来自队列1中CRC患者的186份血清和154份匹配组织样本中的miR-203表达。接下来，我们对来自独立队列（队列2）中的144名CRC患者的血清中的miR-203水平进行了验证。建立CRC相关转移的小鼠模型以鉴定循环miR-203的来源。通过原位杂交确定组织中miR-203的表达模式。与匹配的pCRC组织相比，miR-203表达在LM中显著上调。血清miR-203水平以阶段依赖性方式显著上调，并且在两个患者队列中，高miR-203表达与CRC患者的不良生存相关。血清中miR-203水平的增加表明预后不良（HR=2.1）以及转移至淋巴结（OR=2.5）、肝脏（OR=6.2）、腹膜（OR=7.2）和远处器官（OR=4.4）的高风险。与对照相比，具有肝脏或全身转移的动物中的血清miR-203水平显著更高。高水平的血清miR-203与较差的生存和转移相关，表明其是转移性CRC患者中有希望的非侵入性预后和转移预测生物标志物。
Distant metastasis is a major cause of deaths in CRC patients, which is partly due to lack of robust metastasis-predictive biomarkers. In spite of the important function of miR-203 in cancer metastasis, its clinical significance in CRC metastasis remains unknown. Here, we evaluated the potential role of serum miR-203 as a non-invasive biomarker for CRC metastasis. MiR-203 expression was quantified by qRT-PCR in 58 pairs of primary CRC (pCRC) and corresponding matched liver metastasis (LM), as well as 186 serum and 154 matched tissue specimens from CRC patients in Cohort 1. Next, we performed validation of miR-203 levels in serum from 144 CRC patients in an independent cohort (Cohort 2). A mouse model of CRC-associated metastases was established to identify the source of circulating miR-203. Expression patterns of miR-203 in tissues were determined by in situ hybridization. MiR-203 expression was significantly upregulated in LM compared to matched pCRC tissues. Serum miR-203 levels were significantly up-regulated in a stage-dependent manner, and high miR-203 expression was associated with poor survival in CRC patients in both patient cohorts. Increased miR-203 levels in serum indicated high risk for poor prognosis (HR=2.1), as well as metastasis to lymph nodes (OR=2.5), liver (OR=6.2), peritoneum (OR=7.2), and distant organs (OR=4.4). Serum miR-203 levels were significantly higher in animals with liver or systemic metastasis compared to controls. High levels of serum miR-203 associate with poor survival and metastasis, suggesting it to be a promising non-invasive prognostic and metastasis-predictive biomarker in patients with metastatic CRC.