机构：[1]Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry, Department of Liver Surgery and Liver Transplant of Zhongshan Hospital, Liver Cancer Institute of Fudan University, Fudan University, Shanghai 200032, China.[2]Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China.[3]Department of Gastroenterology, The First People’s Hospital of Yunnan Province, 157 Jin Bi Road, Kunming, Yunnan 650032, China内科片消化内科云南省第一人民医院
Recent reports show that B7-H4 is highly expressed in a variety of tumor cells, functions as a negative regulator of T cells and then promotes tumor progression. However, its expression and role in intrahepatic cholangiocarcinoma (ICC) remain unclear. In present study, B7-H4 expression in ICC and peritumoral tissues was determined at the level of mRNA and protein, and its bioactivity in ICC cells was studied after modification of B7-H4 expression. Then, the mechanism related to tumor progression induced by B7-H4 expression in ICC cells was explored. Finally, clinical significance of B7-H4 expression in ICC patients was further analyzed. The results showed that B7-H4 expression in ICC was much higher than that in peritumoral tissues at the level of both mRNA and protein. The high level of B7-H4 in ICC cells induced epithelial-to-mesenchymal transitions and promoted invasion and metastasis of tumor cells through activation of ERK1/2 signaling. The elevated B7-H4 expression was associated with the downregulated Bax, upregulated Bcl-2 expression, and activation of caspase-3. Clinically, high B7-H4 expression in tumor samples was significantly related to malignant phenotype, such as lymph node metastasis, high tumor stage, and poor differentiation. ICC patients with high expression of B7-H4 had shorter overall survival (OS) and disease-free survival Moreover, the B7-H4 expression was an independent prognostic factor for predicting OS and tumor recurrence of ICC patients after operation. In conclusion, high expression of B7-H4 promotes tumor progression of ICC and may be a novel therapeutic target for ICC patients.
基金：
National Natural Science Foundation of China
(81602513, 81472840, 81160062, 81272295, 81672825, and 81302100) and the
Shanghai Municipal Natural Science Foundation (14ZR1405800 and
17ZR1405400), Zhongshan Hospital Outstanding Youth Fund (2015ZSYXQN03),
Foundation for University Teacher by the Ministry of Education of China
(20120071120068), and the Yunnan Applied Basic Research Projects-Kunming
Medical University Union Foundation (2013FZ271 and 2014FB053), and the
Construction Project of the Second Affiliated Hospital of Kunming Medical
University, Yunnan Province, Internal Organs-construction Projects (2016NS248,
2017NS281, 2017NS282, and 2017NS283).
第一作者机构：[1]Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry, Department of Liver Surgery and Liver Transplant of Zhongshan Hospital, Liver Cancer Institute of Fudan University, Fudan University, Shanghai 200032, China.[2]Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Xie Nan,Cai Jia-Bin,Zhang Lu,et al.Upregulation of B7-H4 promotes tumor progression of intrahepatic cholangiocarcinoma[J].CELL DEATH & DISEASE.2017,8:doi:10.1038/s41419-017-0015-6.
APA：
Xie, Nan,Cai, Jia-Bin,Zhang, Lu,Zhang, Peng-Fei,Shen, Ying-Hao...&Shi, Guo-Ming.(2017).Upregulation of B7-H4 promotes tumor progression of intrahepatic cholangiocarcinoma.CELL DEATH & DISEASE,8,
MLA：
Xie, Nan,et al."Upregulation of B7-H4 promotes tumor progression of intrahepatic cholangiocarcinoma".CELL DEATH & DISEASE 8.(2017)
生物学