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.
Highlights
Recent reports show that B7-H4 is highly expressed in a variety of tumor cells, functions as a negative regulator of T cells and promotes tumor progression
B7-H4 was highly expressed in intrahepatic cholangiocarcinoma (ICC) tissues Here we first detected the B7-H4 expression in tumor tissues and their corresponding adjacent non-tumor tissues from 35 ICC patients by quantitative real-time PCR and western blotting
The results showed that positive staining for B7-H4 protein was mainly localized in the cell membrane of tumor cells and its intensity in tumor tissues was stronger than that in corresponding adjacent nontumor tissues (Fig. 1d, e)
Summary
Recent reports show that B7-H4 is highly expressed in a variety of tumor cells, functions as a negative regulator of T cells and promotes tumor progression. 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. The mechanism related to tumor progression induced by B7-H4 expression in ICC cells was explored. 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. High expression of B7-H4 promotes tumor progression of ICC and may be a novel therapeutic target for ICC patients.
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