Annexin A8 Is a Prognostic Marker and Potential Therapeutic Target for Pancreatic Cancer

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Abstract

Objectives

We investigated whether annexin A8 (A-A8), a Ca2+-binding protein overexpressed in pancreatic cancer, plays a role in cell growth and migration and investigated its association with pancreatic cancer prognosis.

Methods

Clinicopathological features and associations between increased A-A8 expression (determined by immunohistochemistry) and histologic grade were studied in a tissue microarray of 90 patients with resected stage I/II pancreatic cancer. We investigated A-A8’s effect on cell migration, proliferation, and colony formation in 2 pancreatic cancer cells (BXPC-3 and Panc-1). Statistical analyses included Fisher exact test, t test, analysis of variance, and survival analysis.

Results

Western blot showed increased A-A8 expression in human pancreatic cancer cells, with A-A8 knockdown in BXPC-3 and Panc-1 cells demonstrating decreased cell viability (P = 0.017 and P = 0.001), migration (2.5 vs 0.9 mm and 1.6 vs 1 mm at 96 hours; P = 0.048 and P = 0.004), and colony formation (approximately 75% and 40% from scramble; P ≤ 0.01), respectively. In our tissue microarray, A-A8 expression increased 5.9-fold (r = 0.31; P = 0.019) from low- to high-grade tumors, correlating with tumor grade (r = 0.23; P = 0.027). In addition, high A-A8 expression was associated with a decreased 5-year survival (P = 0.042).

Conclusions

Our study is the first showing that increased A-A8 expression is associated with poor prognosis in early-stage pancreatic cancer, thus supporting its further investigation as a future therapeutic target and prognostic marker.

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