Upregulation of B7-H4 promotes tumor progression of intrahepatic cholangiocarcinoma.

Abstract:

: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.

journal_name

Cell Death Dis

journal_title

Cell death & disease

authors

Xie N,Cai JB,Zhang L,Zhang PF,Shen YH,Yang X,Lu JC,Gao DM,Kang Q,Liu LX,Zhang C,Huang XY,Zou H,Zhang XY,Song ZJ,Sun HX,Fu BM,Ke AW,Shi GM

doi

10.1038/s41419-017-0015-6

subject

Has Abstract

pub_date

2017-12-13 00:00:00

pages

3205

issue

12

issn

2041-4889

pii

10.1038/s41419-017-0015-6

journal_volume

8

pub_type

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