MicroRNA profiles discriminate among colon cancer metastasis

Alessandra Drusco, Gerard J. Nuovo, Nicola Zanesi, Gianpiero Di Leva, Flavia Pichiorri, Stefano Volinia, Cecilia Fernandez, Anna Antenucci, Stefan Costinean, Arianna Bottoni, Immacolata A. Rosito, Chang Gong Liu, Aaron Burch, Mario Acunzo, Yuri Pekarsky, Hansjuerg Alder, Antonio Ciardi, Carlo M. Croce

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article numbere96670
JournalPLoS One
Volume9
Issue number6
DOIs
Publication statusPublished - Jun 12 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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