Carbonic anhydrase IX, hypoxia-inducible factor-1α, ezrin and glucose transporter-1 as predictors of disease outcome in rectal cancer: multivariate Cox survival models following data reduction by principal component analysis of the clinicopathological predictors.

Strong expression of carbonic anhydrase IX (CAIX), hypoxia-inducible factor-1α (HIF-1α), ezrin and glucose transporter-1 (GLUT-1) was previously shown to be related to adverse disease outcome in rectal cancer. In this study, operative samples of 178 rectal cancer patients 77 treated with short-course and 47 with long-course preoperative radiotherapy (RT), and 54 with no preoperative treatment, as well as 80 preoperative biopsies from the RT group patients were analyzed for these markers. For data reduction, principal component analysis (PCA) was used to extract a set of factors from the original clinicopathological variables that would explain as much as possible of their variance. After extraction and promax rotation, this set of five first-order factors (F1-F5) was used in multivariate (Cox) modeling together with the four biomarkers. In model 1 (biomarkers in operative samples), F1 was the only independent determinant of disease-free (DFS) (p=0.043) and disease-specific survival (DSS) (p=0.029). In model 2 (biomarkers in preoperative biopsies), none of the five factors or biomarkers were significantly associated with DFS. However, HIF-1α (p=0.024), ezrin (p=0.034), F1 (p=0.011), and F3 (p=0.001) were significant independent predictors of DSS. Similarly, in model 3 (ezrin in preoperative biopsies and others in operative samples), none of the factors or biomarkers were significant predictors of DFS. However, CAIX (p=0.028), and F1 (p= 0.017) were significantly associated with DSS. Preoperative RT markedly modifies the expression of these four biomarkers and also interferes with the original clinicopathological prognosticators (loaded to F1-F5), emphasizing the complexity of prognostication in rectal cancer.