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.
Highlights
Pancreatic cancer is one of the most fatal malignancies, while the five-year survival rate of about only 5% [1]
Our results revealed B7-H4 to be associated with poor prognosis in patients with pancreatic cancer liver metastasis
B7‐H4 is a significant costimulatory molecule responsible for T cell inactivation [20], which is widely expressed in many tumor tissues and possibly acts as a negative regulatory factor in anti-tumor immune response [23, 24]
Summary
Pancreatic cancer is one of the most fatal malignancies, while the five-year survival rate of about only 5% [1]. Occult liver metastases may already have been present at the time of surgery are one of the most common sites of treatment failure and are associated with poor prognosis [3,4,5,6,7]. The median survival time of patients with pancreatic cancer liver metastases is < 6 months [8,9,10,11]. We should pay more attention on liver metastases to define the mechanisms www.impactjournals.com/oncotarget of them and to identify patients with pancreatic cancer who have great risk of progressing them [12]
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