Genetic and immunohistochemical expression of integrins ITGAV, ITGA6, and ITGA3 as prognostic factor for colorectal cancer: Models for global and disease-free survival

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Abstract

© 2015 Linhares et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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 hypoor hyperexpression status of each marker. The log-rank test was used to verify whether the differences were significant. Stepwise C ox 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.

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Linhares, M. M., Affonso, R. J., De Souza Viana, L., Silva, S. R. M., Denadai, M. V. A., De Toledo, S. R. C., & Matos, D. (2015). 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). https://doi.org/10.1371/journal.pone.0144333

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