Thrombospondin 2 is a Functional Predictive and Prognostic Biomarker for Triple-Negative Breast Cancer Patients With Neoadjuvant Chemotherapy.

Abstract

Background: Triple-negative breast cancer (TNBC) is characterized by a more aggressive biological behavior and unfavorable outcome. Circulating and histological expression of THBS2 has been demonstrated to be a novel diagnostic and prognostic biomarker in patients with various types of tumors. However, few studies have evaluated the predictive and prognostic value of THBS2 in TNBC specifically. Methods: In total, 185 triple-negative breast cancer patients (TNBC) with preoperative neoadjuvant chemotherapy were enrolled in this study. Serum THBS2 (sTHBS2) level was measured both prior to the start of NAC and at surgery by enzyme-linked immunosorbent assay (ELISA). Histological THBS2 (hTHBS2) expression in patients with residual tumors was evaluated by immunohistochemistry (IHC) staining method. Correlations between variables and treatment response were studied. Kaplan-Meier plots and Cox proportional hazard regression model were applied for survival analysis. Functional activities of THBS2 in TNBC cells were determined by CCK-8 assay, colony formation, wound healing, and transwell assay. Results: Of the 185 patients, 48 (25.9%) achieved pathological complete response (pCR) after completion of NAC. Elevated pCR rates were observed in patients with a lower level of sTHBS2 at surgery and higher level of sTHBS2 change (OR = 0.88, 95%CI: 0.79-0.98, p = 0.020 and OR = 1.12, 95%CI: 1.02-1.23, p = 0.015, respectively). In survival analysis, hTHBS2 expression in residual tumor was of independent prognostic value for both disease-free survival (HR = 2.21, 95%CI = 1.24-3.94, p = 0.007) and overall survival (HR = 2.07, 95%CI = 1.09-3.92, p = 0.026). For functional studies, THBS2 was indicated to inhibit proliferation, migration, and invasion abilities of TNBC cells in vitro. Conclusion: Our findings confirmed the value of serum THBS2 level to predict pCR for TNBC patients and the prognostic performance of histological THBS2 expression in non-pCR responders after NAC. THBS2 might serve as a promising functional biomarker for patients with triple-negative breast cancer.