title: MicroRNA profiles discriminate among colon cancer metastasis.
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.
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Drusco
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nuovo
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Nicola
authors.initials: N
authors.lastname: Zanesi
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Di Leva
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Flavia
authors.initials: F
authors.lastname: Pichiorri
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America; Dept. of Morphology, Surgery and Experimental Medicine, Universita' degli Studi, Ferrara, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Fernandez
authors.affiliation: UOSD of Clinical Pathology, Regina Elena Institute, Rome, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Antenucci
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Costinean
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Arianna
authors.initials: A
authors.lastname: Bottoni
authors.affiliation: UOSD of Clinical Pathology, Regina Elena Institute, Rome, Italy.
authors.forename: Immacolata A
authors.initials: IA
authors.lastname: Rosito
authors.affiliation: Dept. Experimental therapeutic-unit 1950, The University of Texas, MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Chang-Gong
authors.initials: CG
authors.lastname: Liu
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Aaron
authors.initials: A
authors.lastname: Burch
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Mario
authors.initials: M
authors.lastname: Acunzo
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Pekarsky
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Hansjuerg
authors.initials: H
authors.lastname: Alder
authors.affiliation: Dep. of Radiologic and Oncologic Sciences and Pathology, University of Rome "La Sapienza", Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ciardi
authors.affiliation: MVIMG, Ohio State University, Columbus, Ohio, United States of America.
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D008207:Lymphatic Metastasis; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs