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. 2016 Nov 1;7(44):72242-72249.
doi: 10.18632/oncotarget.12665.

Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases

Yun Qian  1 , Yiwen Sang  1 , Frederick X C Wang  2 , Bo Hong  3 , Qi Wang  1 , Xinhui Zhou  4 , Tianhao Weng  5 , Zhigang Wu  5 , Min Zheng  5 , Hong Zhang  6 , Hangping Yao  5
Affiliations

Prognostic significance of B7-H4 expression in matched primary pancreatic cancer and liver metastases

Yun Qian et al. Oncotarget. .

Abstract

Liver metastasis development in pancreatic cancer patients is common and confers a poor prognosis. Clinical relevance of biomarker analysis in metastatic tissue is necessary. B7-H4 has an inhibitory effect on T cell mediated response and may be involved in tumor development. Although B7-H4 expression has been detected in pancreatic cancer, its expression in liver metastases from pancreatic cancer is still unknown. In this study, overall 43 pancreatic cancer liver metastases (with matched primaries in 15/43 cases) and 57 pancreatic cancer cases without liver metastases or other distant metastases were analyzed for their expression of B7-H4 by immunohistochemistry. Survival curves and log-rank tests were used to test the association of B7-H4 expression with survival. B7-H4 was highly expressed in 28 (65.1%) of the 43 liver metastases and 9 (60.0%) of the 15 matched primary tumors. The expression of B7-H4 in liver metastases was significantly higher than in the matched primary tumors (p < 0.05). Patients with high B7-H4 expression in their primary pancreatic cancer had higher risk of developing liver metastases (p < 0.05). In univariate analysis, B7-H4 expression was significantly associated with the risk of death (p < 0.05). And the multivariate analysis identified that B7-H4 was an independent prognostic indicator (p < 0.05). Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis. B7-H4 may promote pancreatic cancer metastasis and was promising to be a potential prognostic indicator of pancreatic cancer.

Keywords: B7-H4; immunohistochemistry; liver metastases; pancreatic cancer; survival analysis.

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that they have no conflict of interest related to the publication of this manuscript.

Figures

Figure 1
Figure 1. B7-H4 expression in liver metastases from pancreatic cancer
(A) weak staining (staining intensity score = 1); (B) moderate staining (staining intensity score = 2); (C) strong staining (staining intensity score = 3). Enhanced B7-H4 expression in liver metastases (E) as compared with the matched primary pancreatic cancer (D) Note: Magnification for all photomicrographs is ×400.
Figure 2
Figure 2. Differential expression of B7-H4 in liver metastases and primary pancreatic tumors
The immunohistochemical score of B7-H4 expression in the liver metastases was higher than in the matched primary pancreatic cancer in 15 paired cases (p < 0.05). And the immunohistochemical score of B7-H4 expression in the matched primary pancreatic cancer was higher than in the control group (p < 0.05).
Figure 3
Figure 3. Kaplan–Meier analysis showing that patients with liver metastases with high B7-H4 expression had shorter survival than those with low expression (p < 0.05)
See this image and copyright information in PMC

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