Abstract:Background and Aims: Triple negative breast cancer (TNBC) has an extremely poor prognosis because of the lack of effective therapeutic targets and limited treatment options in clinical practice. This study was designated to investigate the expression of FAT atypical cadherin 4 (FAT4) in TNBC tissue and its clinical significance, so as to provide a new treatment strategy for this disease.
Methods: The mRNA and protein expressions of FAT4 in fresh paired tumor and adjacent tissue samples from 10 TNBC patients were determined by RT-PCR and Western blot, respectively. Then, FAT4 expressions in the paraffin-embedded specimens of paired tumor and adjacent tissue from 60 TNBC patients were examined by immunohistochemical staining, and the relations of FAT4 expression with the clinicopathologic features and prognosis of the TNBC patients were analyzed.
Results: In the 10 paired fresh tissue samples, the relative expression levels of FAT4 mRNA and protein were significantly lower in TNBC tissue than those in adjacent tissue (both P<0.05), using adjacent tissue as a reference, the mRNA expression value was 0.482±0.092 and protein expression value was 0.437±0.082 respectively. In the 60 paraffin-embedded specimens, the positive expression rate of FAT4 protein in TNBC tissue was significantly lower than that in adjacent tissue (23.33% vs. 71.67%, χ2=28.104, P<0.001); the FAT4 protein expression was significantly associated with lymph node status (P=0.034), tumor size (P=0.001), TNM stage (P=0.028), histological grade (P=0.023) and Ki-67 index (P=0.031), but irrelevant to age (P=0.744) and menstrual status (P=0.933); the disease-free survival (DFS) in TNBC patients with positive FAT4 expression was significantly longer than that in those with negative FAT4 expression (42.0 months vs. 34.6 months, P=0.037); Cox multivariate proportional hazard model shown that high FAT4 expression of was an independent protective factor for DFS in TNBC patients (HR=0.52, 95% CI=0.29–0.98, P=0.041).
Conclusion: FAT4 expression is decreased in TNBC tissue, and low FAT4 expression is closely related to the malignant biological characteristics and unfavorable outcomes of TNBC patients.