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Genetic and Immunohistochemical Expression of Integrins ITGAV, ITGA6, and ITGA3 As Prognostic Factor for Colorectal Cancer: Models for Global and Disease-Free Survival

Authors: Marcelo Moura Linhares; Marcelo Moura Linhares; Renato José Affonso; Luciano de Souza Viana; Sandra Regina Morini Silva; Marcos Vinicius Araujo Denadai; Silvia Regina Caminada de Toledo; +1 Authors

Genetic and Immunohistochemical Expression of Integrins ITGAV, ITGA6, and ITGA3 As Prognostic Factor for Colorectal Cancer: Models for Global and Disease-Free Survival

Abstract

To evaluate the relationship between the expression profiles of 84 extracellular matrix (ECM) genes and the prognosis of patients with colorectal cancer (CRC).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.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.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.

Keywords

Adult, Male, Integrin alpha3, Science, Kaplan-Meier Estimate, Integrin alpha6, Biomarkers, Tumor, Humans, Neoplasm Metastasis, Aged, Neoplasm Staging, Proportional Hazards Models, Extracellular Matrix Proteins, Gene Expression Profiling, Q, R, Integrin alphaV, Middle Aged, Prognosis, Gene Expression Regulation, Neoplastic, Medicine, Female, Neoplasm Grading, Colorectal Neoplasms, Research Article

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
33
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Top 10%
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