Genetic and Immunohistochemical Expression of Integrins ITGAV, ITGA6, and ITGA3 As Prognostic Factor for Colorectal Cancer: Models for Global and Disease-Free Survival.
PLoS One
; 10(12): e0144333, 2015.
Article
em En
| MEDLINE
| ID: mdl-26674523
OBJECTIVE: To evaluate the relationship between the expression profiles of 84 extracellular matrix (ECM) genes and the prognosis of patients with colorectal cancer (CRC). METHODS: This retrospective study included 114 patients with stage I-IV CRC who underwent primary tumour resection. Quantitative real-time PCR and immunohistochemistry assays were conducted using primary tumour samples. Kaplan-Meier survival curves were also generated to identify differences in global survival (GS) and disease-free survival (DFS) for the hypo- or hyperexpression status of each marker. The log-rank test was used to verify whether the differences were significant. Stepwise Cox regression models were also used to identify the risk factors associated with GS and DFS in a multivariate mode, and then were used to score the risk of death associated with each marker, either independently or in association. RESULTS: In the univariate analyses, significant differences in GS in relation to the expression profiles of ITGAV (p = 0.001), ITGA3 (p = 0.002), ITGA6 (p = 0.001), SPARC (p = 0.036), MMP9 (p = 0.034), and MMP16 (p = 0.038) were observed. For DFS, significant differences were observed in associated with ITGAV (p = 0.004) and ITGA3 (p = 0.001). However, only the ITGAV and ITGA6 gene markers for GS (hazard ratio (HR) = 3.209, 95% confidence interval (CI) = 1.412-7.293, p = 0.005 and HR = 3.105, 95% CI = 1.367-7.055, p = 0.007, respectively), and ITGA3 for DFS (HR = 3.806, 95% CI = 1.573-9.209, p = 0.003), remained in the final Cox regression models. A scoring system was developed to evaluate the risk of patient death based on the number of markers for the components of the final GS model. Scores of 0, 1, or 2 were associated with the following mean survival rates [CI]: 47.162 [44.613-49.711], 39.717 [35.471-43.964], 30.197 [24.030-36.327], respectively. CONCLUSIONS: Multivariate mathematical models demonstrated an association between hyperexpression of the ITGAV and ITGA6 integrins and GS, and also between the ITGA3 integrin and DFS, in patients with colorectal tumours. A risk scoring system based on detected hyperexpression of 0, 1, or 2 markers (e.g., ITGAV and/or ITGA6) was also found to accurately correlate with the GS curves generated for the present cohort.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
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Integrina alfa3
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Integrina alfa6
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Integrina alfaV
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos