MiR-139-5p as a novel serum biomarker for recurrence and metastasis in colorectal cancer.
MiR-139-5p as a novel serum biomarker for recurrence and metastasis in colorectal cancer.
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DOI：
10.1038/srep43393
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发表时间：
2017-03-06
影响因子：
4.6
通讯作者：
Goel A
中科院分区：
文献类型：
--
作者：
Miyoshi J;Toden S;Yoshida K;Toiyama Y;Alberts SR;Kusunoki M;Sinicrope FA;Goel A
大约 30-50% 接受根治性切除的结直肠癌 (CRC) 患者随后会出现肿瘤复发或转移。尽管 microRNA (miRNA) 是一类小非编码 RNA，在各种人类恶性肿瘤中经常失调，但仍不清楚它们是否有助于预测 CRC 患者的复发和转移。最初使用 miRNA 微阵列和 miRNA-seq 数据集筛选有或没有复发的 miRNA。然后在两个独立队列中测试候选 miRNA，其中包括 111 名 II/III 期和 139 名 I-III 期 CRC 患者，以及血清样本和匹配的原发性和转移性肝组织。使用腹膜传播的动物模型来评估目标 miRNA 的致癌作用。在初步筛选过程中确定了四种候选 miRNA，随后我们在两个独立的临床队列中验证了 miR-139-5p 的上调，其中它与较差的无复发生存率相关。此外，复发阳性 CRC 患者血清中的 miR-139-5p 也上调，并且无复发生存期显着缩短。有趣的是，miR-139-5p 在转移性肝组织中表达上调，并与上皮间质转化相关基因呈负相关。最后，我们发现 miR-139-5p 过表达增强了小鼠模型中的腹膜传播。总之，我们将 miR-139-5p 确定为结直肠癌肿瘤复发和转移的新型生物标志物。
Approximately 30–50% of colorectal cancer (CRC) patients who undergo curative resection subsequently experience tumor recurrence or metastasis. Although microRNAs (miRNAs) are a class of small noncoding RNAs frequently deregulated in various human malignancies, it remains unknown if these can help predict recurrence and metastasis in CRC patients. MiRNAs were initially screened using miRNA-microarray and miRNA-seq datasets with or without recurrence. Candidate miRNAs were then tested in two independent cohorts of 111 stage II/III and 139 stage I-III CRC patients, as well as serum samples and matched primary and metastatic liver tissues. An animal model of peritoneal dissemination was used to assess the oncogenic role of the target miRNA. Four candidate miRNAs were identified during the initial screening, and we subsequently validated upregulation of miR-139-5p in two independent clinical cohorts, wherein it associated with poor recurrence-free survival. Moreover, miR-139-5p were also upregulated in the serum of recurrence-positive CRC patients and yielded significantly shorter recurrence-free survival. Intriguingly, miR-139-5p was upregulated in metastatic liver tissues and negatively correlated with genes associated with epithelial-mesenchymal transition. Lastly, we showed that miR-139-5p overexpression enhanced peritoneal dissemination in a mouse model. In conclusion, we identified miR-139-5p as a novel biomarker for tumor recurrence and metastasis in CRC.