Down-regulated FST expression is involved in the poor prognosis of triple-negative breast cancer

Cancer Cell International

Bin Liu¹  Yong Li²  Sainan Liu²  Yawen Liu²  Qian Zhao²  Jikang Shi²  Yanbo Guo²  Yulu Gu²  Yichun Qiao²  Yi Cheng³  Yunkai Liu³ 

[1] Department of Breast Surgery, Second Affiliated Hospital of Jilin University, 130021, Changchun, China;Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, 130021, Changchun, China;Institute of Translational Medicine, The First Hospital of Jilin University, 130021, Changchun, China;

关键词: Follistatin;    Triple-negative breast cancer;    Prognosis biomarker;    Proliferation;    Migration;    Invasion;   

DOI  :  10.1186/s12935-021-01977-x

来源: Springer

【 摘 要 】

BackgroundTriple-negative breast cancer (TNBC) is more commonly associated with young patients, featuring high histological grade, visceral metastasis, and distant recurrence. Follistatin (FST) is a secreted extracellular regulatory protein that antagonizes TGF-β superfamily such as activin and TGF-β related superfamily such as bone morphogenetic protein (BMP). The implication of FST in the proliferation, angiogenesis, and metastasis of solid tumors documents good or poor outcome of patients with BC. However, the role of FST in TNBC remains unclear.MethodsData of 935 patients with breast cancer (BC) were extracted from TCGA. Case–control study, Kaplan–Meier, uni-multivariate COX, and ROC curve were utilized to investigate the relationship between FST expression and the clinical characteristics and prognosis of BC. Functional studies were used to analyze the effect of FST expression on proliferation, apoptosis, migration, and invasion of TNBC cell lines. Bioinformatic methods such as volcanoplot, GO annd KEGG enrichment, and protein–protein interactions (PPI) analyses were conducted to further confirm the different roles of FST in the apoptotic pathways among mesenchymal and mesenchymal stem-like cells of TNBC.ResultsData from TCGA showed that low FST expression correlated with poor prognosis (for univariate analysis, HR = 0.47, 95% CI: 0.27–0.82, p = 0.008; for multivariate analysis, HR = 0.40, 95% CI: 0.21–0.75, p = 0.004). Low FST expression provided high predicted value of poor prognosis in TNBC amongst BCs. FST knockdown promoted the proliferation, migration and invasion of BT549 and HS578T cell lines. FST inhibited the apoptosis of mesenchymal cells by targeting BMP7.ConclusionsLow FST expression is associated with poor prognosis of patients with TNBC. FST expressions exhibit the anisotropic roles of apoptosis between mesenchymal and mesenchymal stem-like cells but promote the proliferation, migration, invasion in both of two subtypes of TNBC in vitro. FST may be a subtype-heterogeneous biomarker for monitoring the progress of TNBC.

【 授权许可】

CC BY