Growth differentiation factor-15 and lactoferrin immuno-expression in breast cancer: relationship with body iron-status and survival outcome

We aimed to evaluate the expression of growth differentiation factor-15 (GDF-15) and lactoferrin (Lf) in tumor and their relationship with the body iron-status and overall survival (OS) outcome of patients with breast cancer. A retrospective cohort study of female patients with primary breast cancer was performed. Clinical tumor samples from the Second Affiliated Hospital of Soochow University between December 2008 and June 2014 were collected. The immuno-expression of GDF-15 and Lf was stratified into positive or negative expression. Kaplan-Meier method and Cox proportional hazards regression model were used for data analysis. 74 breast cancer patients with a mean age of 52 years were included into our study. 14 (18.9%) patients were died by the end of August 1, 2019. The serum iron level of patients with GDF-15 (+)/Lf(-) expression was higher than that of patients with other expression patterns (18.2 +/- 5.4 vs. 15.5 +/- 5.0 mu mol/L, P = 0.038), but was not associated with OS. In univariate Cox analyses, GDF-15(+) and GDF-15(+)/Lf(-) were significantly correlated with high mortality risk (HR = 3.75, 95%CI 1.05-13.48, P = 0.025; HR = 5.00, 95%CI 1.56-16.04, P = 0.004, respectively). After adjusted for age, menopause status and primary tumor grade, the association between GDF-15 and OS disappeared. However, the association between GDF-15/Lf and OS still existed in GDF-15(+)/Lf(-) (HR = 4.50, 95%CI 1.31-15.51, P = 0.017). The combined immuno-expression pattern of GDF-15 and Lf was significant associated with high serum iron level. GDF-15/Lf could be a powerful biomarker to predict survival outcome of patients with breast cancer but still needed to be confirmed by future studies.