MicroRNA profiles discriminate among colon cancer metastasis.

MicroRNA profiles discriminate among colon cancer metastasis.
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DOI:
10.1371/journal.pone.0096670
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Croce CM
Croce CM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Drusco A;Nuovo GJ;Zanesi N;Di Leva G;Pichiorri F;Volinia S;Fernandez C;Antenucci A;Costinean S;Bottoni A;Rosito IA;Liu CG;Burch A;Acunzo M;Pekarsky Y;Alder H;Ciardi A;Croce CM

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MicroRNA正被用于癌症和其他疾病的诊断、预后和监测。它们的高组织特异性和在肿瘤发生中的关键作用为癌症的诊断和分类以及预测患者的结果提供了新的生物标志物。已经在许多人类肿瘤中鉴定了microRNA特征,包括结直肠癌(CRC)。在大多数情况下,转移性疾病很难预测,也很难通过适当的治疗来预防。我们研究的目的是确定转移性CRC的microRNA特征,可以预测和区分转移性靶器官定位。分析了三组不同CRC患者的正常和癌组织。RNA微阵列和TaqMan阵列分析进行了66例意大利患者或没有淋巴结和/或肝复发。分别分析用两种测定法获得的数据,然后重复分析以鉴定原发性CRC转移特征。通过qRT-PCR对第二组16名美国转移性患者的5种差异表达的microRNA(hsa-miR-21、-103、-93、-31和-566)进行了验证。原位杂交进行了16名美国患者,以及三个不同的商业组织芯片(TMA)包含正常相邻的结肠,原发性腺癌,正常和转移淋巴结和肝脏。hsa-miRNA-21、-93和-103上调与hsa-miR-566下调共同定义了CRC转移特征,而原位杂交数据确定了淋巴结侵袭特征。我们提供了第一个可以区分结直肠淋巴结和肝脏复发以及结直肠肝转移和原发性肝肿瘤的microRNA特征。
MicroRNAs are being exploited for diagnosis, prognosis and monitoring of cancer and other diseases. Their high tissue specificity and critical role in oncogenesis provide new biomarkers for the diagnosis and classification of cancer as well as predicting patients' outcomes. MicroRNAs signatures have been identified for many human tumors, including colorectal cancer (CRC). In most cases, metastatic disease is difficult to predict and to prevent with adequate therapies. The aim of our study was to identify a microRNA signature for metastatic CRC that could predict and differentiate metastatic target organ localization. Normal and cancer tissues of three different groups of CRC patients were analyzed. RNA microarray and TaqMan Array analysis were performed on 66 Italian patients with or without lymph nodes and/or liver recurrences. Data obtained with the two assays were analyzed separately and then intersected to identify a primary CRC metastatic signature. Five differentially expressed microRNAs (hsa-miR-21, -103, -93, -31 and -566) were validated by qRT-PCR on a second group of 16 American metastatic patients. In situ hybridization was performed on the 16 American patients as well as on three distinct commercial tissues microarray (TMA) containing normal adjacent colon, the primary adenocarcinoma, normal and metastatic lymph nodes and liver. Hsa-miRNA-21, -93, and -103 upregulation together with hsa-miR-566 downregulation defined the CRC metastatic signature, while in situ hybridization data identified a lymphonodal invasion profile. We provided the first microRNAs signature that could discriminate between colorectal recurrences to lymph nodes and liver and between colorectal liver metastasis and primary hepatic tumor.
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