A Novel Prognostic Model Based on the Serum Iron Level for Patients With Early-Stage Triple-Negative Breast Cancer

Abstract

The dysregulation of iron homeostasis has been explored in malignancies. However, studies focusing on the association between the serum iron level and prognosis of patients with early-stage triple-negative breast cancer (TNBC) are scarce. Accordingly, in current study, 272 patients with early-stage TNBC treated at Sun Yat-sen University Cancer Center (SYSUCC) between September 2005 and October 2016 were included as a training cohort, another 86 patients from a previous randomized trial, SYSUCC-001, were analyzed as a validation cohort (SYSUCC-001 cohort). We retrospectively collected their clinicopathological data and tested the serum iron level using blood samples at the diagnosis. In the training cohort, patients were divided into low-iron and high-iron groups according to the serum iron level cut-off of 17.84 μmol/L determined by maximally selected rank statistics. After a median follow-up of 87.10 months, patients with a low iron had a significantly longer median disease-free survival (DFS) of 89.13 [interquartile range (IQR): 66.88–117.38] months and median overall survival (OS) of 92.85 (IQR: 68.83–117.38) months than those in the high-iron group (median DFS: 75.25, IQR: 39.76–105.70 months, P = 0.015; median OS: 77.17, IQR: 59.38–110.28 months, P = 0.015). Univariate and multivariate Cox analysis demonstrated the serum iron level to be an independent predictor for DFS and OS. Then, a prognostic nomogram incorporating the serum iron level, T stage and N stage was developed for individualized prognosis predictions. It had good discriminative ability with a C-index of DFS (0.729; 95% CI 0.666–0.792) and OS (0.739; 95% CI 0.666–0.812), respectively. Furtherly, we validated the predictive model in the SYSUCC-001 cohort, which also showed excellent predictive performance with a C-index of DFS (0.735; 95% CI 0.614–0.855) and OS (0.722; 95% CI 0.577–0.867), respectively. All these suggested that the serum iron level might be a potential prognostic biomarker for patients with early-stage TNBC, the predictive model based on it might be served as a practical tool for individualized survival predictions.

PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype

“…LCN2 is a multifunctional protein primarily known as a siderophore capable of binding and transporting iron, but it also carries various hydrophobic metabolites (e.g., prostaglandins, steroids, and some hormones) as well. Since dysregulated iron homeostasis and a high demand for iron is an unofficial hallmark of cancer [49][50][51], it is plausible to hypothesize that JIMT-1-induced LCN2 upregulation in macrophages may contribute to TAM polarization. Indeed, several lines of evidence in the literature indicate that high levels of LCN2 are associated with a bad prognosis and therapy resistance of breast cancer [52][53][54].…”