Upregulation of B7-H4 promotes tumor progression of intrahepatic cholangiocarcinoma

被引：46

作者：

Xie, Nan ^{[1
,2
]}

Cai, Jia-Bin ^{[1
]}

Zhang, Lu ^{[1
]}

Zhang, Peng-Fei ^{[1
]}

Shen, Ying-Hao ^{[1
]}

Yang, Xuan ^{[1
]}

Lu, Jia-Cheng ^{[1
]}

Gao, Dong-Mei ^{[1
]}

Kang, Qiang ^{[2
]}

Liu, Li-Xin ^{[2
]}

Zhang, Chi ^{[1
]}

Huang, Xiao-Yong ^{[1
]}

Zou, Hao ^{[2
]}

Zhang, Xin-Yu ^{[1
]}

Song, Zheng-Ji ^{[3
]}

Sun, Hai-Xiang ^{[1
]}

Fu, Bi-Mang ^{[2
]}

Ke, Ai-Wu ^{[1
]}

Shi, Guo-Ming ^{[1
]}

机构：

[1] Fudan Univ, Liver Canc Inst, Zhongshan Hosp,Key Lab Carcinogenesis & Canc Inva, Dept Liver Surg & Liver Transplant,Chinese Minist, Shanghai 200032, Peoples R China

[2] Kunming Med Univ, Affiliated Hosp 2, Dept Hepatopancreatobiliary Surg, Kunming 650101, Yunnan, Peoples R China

[3] First Peoples Hosp Yunnan Prov, Dept Gastroenterol, 157 Jin Bi Rd, Kunming 650032, Yunnan, Peoples R China

来源：

CELL DEATH & DISEASE | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

EXPRESSION; CD151; OVEREXPRESSION; INHIBITION; PROGNOSIS; CARCINOMA; PROTEIN; CANCER; CELLS;

D O I：

10.1038/s41419-017-0015-6

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页数：13

共 27 条

[1] Detection of b7-H4 and p53 in pancreatic cancer - Potential role as a cytological diagnostic adjunct [J].