Conclusions
High expression of REG4 is associated with poor therapeutic response, adverse outcome and an aggressive phenotype in rectal cancer patients treated with neoadjuvant CCRT, justifying REG4 is a surrogate marker to predict CCRT resistance.
Methods
REG4 immunohistochemistry was retrospectively assessed for pre-treatment biopsy specimens from 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery without initial distant metastasis. The
Results
High expression of REG4 was associated with advanced pre-treatment nodal status (P = 0.026), advanced post-treatment tumor status (P = 0.006), advanced post-treatment nodal status (P = 0.001), advanced post-treatment tumor stage (P < 0.001), and inferior tumor regression grade (P = 0.001). Of note, high expression of REG4 emerged as an adverse prognosticator for DSS (P = 0.0004), LRFS (P = 0.0009), and MeFS (P = 0.0254). After multivariate comparisons, it remained independently prognostic for worse DSS (hazard ratio [HR] = 2.731; P = 0.025) and LRFS (HR = 2.676; P = 0.029). High expression of REG4 was also negatively associated with γ-H2AX expression (P < 0.0001, r = -0.708). Conclusions: High expression of REG4 is associated with poor therapeutic response, adverse outcome and an aggressive phenotype in rectal cancer patients treated with neoadjuvant CCRT, justifying REG4 is a surrogate marker to predict CCRT resistance.