机构：[1]Department of Orthopedic Oncology, the Third Hospital of Hebei MedicalUniversity, Shijiazhuang, Hebei, People’s Republic of China[2]Departmentof General Surgery, the Fourth Hospital of Hebei Medical University,Shijiazhuang, Hebei, People’s Republic of China河北医科大学第四医院[3]Department of ThoracicSurgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei,People’s Republic of China河北医科大学第四医院[4]Department of Pathology, the Fourth Hospitalof Shijiazhuang, Shijiazhuang, China[5]Department of Liver Diseases, BethuneInternational Peace Hospital, Shijiazhuang, Hebei, People’s Republic of China
Background: The expression of the immunoregulatory protein B7-H4 has been reported in many types of cancer, including breast cancer. However, its role in triple-negative breast cancer (TNBC), especially its correlation with patients' prognosis and chemoresistance remains unclear. Methods: The expression of B7-H4 in TNBC tissues and cell lines were measured with Real-Time PCR and western blotting. 65 cases of TNBC tissue samples and adjacent non-tumor tissue samples were analyzed by immunochemistry to demonstrate the correlation between the B7-H4 expression and clinicopathological characteristics. In vitro studies assessed mAb MIH43 alone and in combination with transfecting B7-H4 siRNA on the growth of chemosensitive and chemoresistant TNBC cell lines by CCK-8 and apoptotic enzyme-linked immunosorbent assay (ELISA). Results: B7-H4 expression was detected positive in 59 of 65 (90.8%) different stage TNBC patients, especially in the samples of recurrence TNBC patients after receiving neoadjuvant chemotherapy treatment. Survival curves showed that patients with B7-H4 overexpression had significantly shorter survival and recurrence time than those with low B7-H4 expression (p < 0.005). Univariate and multivariate COX regression analysis demonstrated that B7-H4 was an independent predictor for advanced tumor stage. The monoclonal antibody of B7-H4 has the potential anti-proliferative effects on inhibiting the chemoresistant TNBC cell lines and increasing the sensitivity of TNBC cell lines to doxorubicin, paclitaxel or carboplatin. RNAi-mediated silencing of B7-H4 in TNBC cells enhanced drug-induced apoptosis via inhibiting PTEN/PI3K/AKT pathway, whereas reexpression of B7-H4 in B7-H4 knockdown and low B7-H4 expressing cells increased the phosphorylation of PI3K and AKT along with restoration of PETN expression. Conclusions: Our data show that B7-H4 is a biomarker indicative of a poor prognosis in TNBC patients and at least partially downregulated in chemoresistance via PTEN/PI3K/AKT pathway. Targeting B7-H4 might provide an attractive therapeutic approach specifically for TNBC patients.
基金：
National Natural Science
Foundation of China (81402228, 81772858), Hebei Natural Science Foundation
(H2015206216), HeBei Province Education Foundation (QN2014049) and
HeBei Province Medical Foundation (ZL20140334, 20160649).
第一作者机构：[1]Department of Orthopedic Oncology, the Third Hospital of Hebei MedicalUniversity, Shijiazhuang, Hebei, People’s Republic of China
通讯作者：
推荐引用方式(GB/T 7714)：
Wang Ling,Yang Chao,Liu Xin-bo,et al.B7-H4 overexpression contributes to poor prognosis and drug-resistance in triple-negative breast cancer[J].CANCER CELL INTERNATIONAL.2018,18:doi:10.1186/s12935-018-0597-9.
APA：
Wang, Ling,Yang, Chao,Liu, Xin-bo,Wang, Li&Kang, Fu-biao.(2018).B7-H4 overexpression contributes to poor prognosis and drug-resistance in triple-negative breast cancer.CANCER CELL INTERNATIONAL,18,
MLA：
Wang, Ling,et al."B7-H4 overexpression contributes to poor prognosis and drug-resistance in triple-negative breast cancer".CANCER CELL INTERNATIONAL 18.(2018)
