AUTHOR=Lin Yuxiang , Lin E. , Li Yan , Chen Xiaobin , Chen Minyan , Huang Jun , Guo Wenhui , Chen Lili , Wu Long , Zhang Xiang , Zhang Wenzhe , Jin Xuan , Zhang Jie , Fu Fangmeng , Wang Chuan 

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

JOURNAL=Pathology and Oncology Research

VOLUME=Volume 28 - 2022

YEAR=2022

URL=https://www.por-journal.com/journals/pathology-and-oncology-research/articles/10.3389/pore.2022.1610559

DOI=10.3389/pore.2022.1610559

ISSN=1532-2807

ABSTRACT=Background: In this study, we investigated the predictive and prognostic value of THBS2 for triple-negative breast cancer (TNBC) patients with neoadjuvant chemotherapy (NAC).
Methods: In total, 185 TNBC patients with preoperative neoadjuvant chemotherapy were enrolled in this study. Serum THBS2 (sTHBS2) level was measured both prior to the start of NAC or 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 was 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: Among all 185 patients, 48 (25.9%) achieved pathological complete response (pCR) after completion of NAC. Elevated pCR rates were observed in patients with 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.