title: Metadherin expression and lung relapse in patients with colorectal carcinoma.
abstract: Colorectal cancer (CRC) is the third most common malignant disease in men and the second in women worldwide. CRC relapse occurs mostly in liver and lungs, decreasing the 5-year survival to 6 %. Metadherin (MTDH) is overexpressed in several types of cancer, has been implicated in proliferation, invasion, metastasis, angiogenesis, and chemoresistance, and is a factor of poor prognosis in CRC. In this work we addressed the prognostic significance of MTDH expression in CRC progression to the lungs. We found that MTDH gene was more frequently amplified (copy number >1.8) in patients with CRC and relapse to the lung, when compared to patients without lung metastases (17.4 vs 100 %; p < 0.001). We observed a correlation between MTDH gene copy number and MTDH expression by IHC (p = 0.0001). Next we also analyzed MTDH expression by IHC in samples from 85 patients diagnosed with CRC, stage II or III, M0, with at least 3 years of follow-up. Kaplan-Meier survival analysis showed that lung relapse-free survival (HR 5.29, 95 % CI 1.90-14.77, p = 0.0004), liver relapse-free survival (HR 8.59, 95 % CI 0.99-74.18, p = 0.003), relapse-free survival (HR 4.85, 95 % CI 1.88-12.45, p = 0.0003) and overall survival (HR 3.75, 95 % CI 1.15-12.18, p = 0.018) were significantly lower in the group with high MTDH expression. Multivariate analysis showed that high MTDH expression was an independent factor for all outcomes. This study demonstrates that high MTDH expression is a biomarker of relapse in CRC, including lung-specific relapse. Determination of MTDH expression in primary CRC may be useful in the earlier detection of lung metastases in patients with high expression and increased risk.
authors.affiliation: Luis Costa Unit, Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Ed. Egas Moniz, Room P3A5, Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal, scasimiro@medicina.ulisboa.pt.
authors.forename: Sandra
authors.initials: S
authors.lastname: Casimiro
authors.forename: Afonso
authors.initials: A
authors.lastname: Fernandes
authors.forename: António Gouveia
authors.initials: AG
authors.lastname: Oliveira
authors.forename: Marco
authors.initials: M
authors.lastname: Franco
authors.forename: Ricardo
authors.initials: R
authors.lastname: Pires
authors.forename: Mafalda
authors.initials: M
authors.lastname: Peres
authors.forename: Margarida
authors.initials: M
authors.lastname: Matias
authors.forename: Joana
authors.initials: J
authors.lastname: Tato-Costa
authors.forename: Nuno
authors.initials: N
authors.lastname: Guerra
authors.forename: Madalena
authors.initials: M
authors.lastname: Ramos
authors.forename: Jorge
authors.initials: J
authors.lastname: Cruz
authors.forename: Luis
authors.initials: L
authors.lastname: Costa
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D016601:RNA-Binding Proteins
chemical_list: D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins