Abstract
Purpose Secreted frizzled-related protein 2 (sFRP2) is a secreted protein associated with cancer drug resistance and metastasis. However, few studies have reported serum sFRP2 levels in breast cancer. We evaluated serum sFRP2 as a potential biomarker for breast cancer. Methods Serum sFRP2 concentrations were detected in 274 breast cancer patients along with 147 normal healthy controls by enzyme-linked immunosorbent assay (ELISA). Diagnostic significance was evaluated by area under the curve (AUC) analysis and the Youden index. Prognostic significance was determined by Kaplan-Meier survival method and univariate and multivariate Cox proportional hazard regression model analyses. Results Serum sFRP2 was elevated in breast cancer patients compared to normal healthy controls (P < 0.001). The sensitivity of sFRP2 in diagnosing breast cancer was 76.9% at a specificity of 76.6%. Elevated serum sFRP2 levels are associated with primary tumor size, TNM stage, and lymph node metastases. The Kaplan-Meier curves showed a significant association of serum sFRP2 with progression-free survival. The multivariate Cox analysis confirmed that high serum sFRP2 was an independent prognostic factor for poor prognosis (HR = 3.89, 95% CI = 1.95-7.68, P = 0.001). Conclusions In conclusion, serum sFRP2 may serve as a potential biomarker for breast cancer diagnosis and prognostic evaluation.
Highlights
Breast cancer is one of the most frequently malignant tumors and a major cause of cancer-related death among women worldwide [1], with an estimated 268,600 newly diagnosed cases and approximately 69,500 deaths annually in China [2]
The study recruited a total of 274 patients who were treated for breast cancer at the First Affiliated Hospital of Sun Yat-sen University and 147 normal healthy controls
Discussion Secreted frizzled-related protein 2 (sFRP2), approximately 300 amino acids in length, belongs to a large family of sFRPs, which are circulating soluble proteins with a highly homologous cysteine-rich domain for cell surface frizzled receptors [13]. sFRP2 is implicated in regulating the Wnt signaling cascade, which plays a vital role in a series of biological processes, including cell proliferation, differentiation, development, cell migration, angiogenesis, Table 4: Univariate and multivariate Cox analysis of variables considered for progression-free survival rates of breast cancer patients
Summary
Breast cancer is one of the most frequently malignant tumors and a major cause of cancer-related death among women worldwide [1], with an estimated 268,600 newly diagnosed cases and approximately 69,500 deaths annually in China [2]. Breast cancer is a heterogeneous disease with four major molecular subtypes: luminal A, luminal B, human epidermal growth factor receptor 2- (HER2-) enriched, and basal-like [3]. Searching for novel and effective biomarkers to detect early stage breast cancer will facilitate the adoption of less aggressive treatments and ameliorate prognosis [5]. Various identified biomarkers, including CA153, CEA, and CA125, have been widely used in breast cancer patients but have limited clinical value due to low sensitivity and specificity [6, 7]. Thence, in addition to improve the early diagnosis and treatment of this heterogeneous disease, novel noninvasive biomarkers for early diagnosis and prognosis are urgently needed
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