title: Specific extracellular matrix remodeling signature of colon hepatic metastases.
abstract: To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier, Montpellier, France ; INSERM, U896, Montpellier, France ; Université Montpellier1, Montpellier, France ; ICM, Institut régional du Cancer Montpellier, Montpellier, France.
authors.forename: Maguy
authors.initials: M
authors.lastname: Del Rio
authors.forename: Caroline
authors.initials: C
authors.lastname: Mollevi
authors.forename: Nadia
authors.initials: N
authors.lastname: Vezzio-Vie
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bibeau
authors.forename: Marc
authors.initials: M
authors.lastname: Ychou
authors.forename: Pierre
authors.initials: P
authors.lastname: Martineau
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000473:pathology*; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger
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