Abstract 1543: Clinical significance of ZNF185 intracellular localization in pancreatic ductal carcinoma

Pancreatic canceris one of the most aggressive human tumors because of the challenges associated with detecting it at an early stage and its high potential for dissemination and distant metastasis. Therefore, clarifying the biological mechanisms underlying distant metastasis from pancreatic cancerand accelerating the development of new treatment strategies are needed. We previously isolated ZNF185, a metastasis-related protein, using a global quantitative proteomeanalysis. ZNF185 contains two zinc-finger motifs in the C-terminus that fit the consensus pattern of the LIM domainsinducing tumor formation and cytoskeleton organization. In the present study, we investigated the expression of ZNF185 in human pancreatic cancerin vivo and in clinical cases, and also evaluated its prognostic significance. Immunohistochemical staining of resected specimens and a xenograft model of liver metastasis was used to examine the relationship between distant metastasis in and the prognosis of pancreatic cancerand the expression of ZNF185. Cells expressing ZNF185 in the plasma membrane were detected in 71 (39.0%) out of 182 patients with resected pancreatic cancer. Patients not expressing ZNF185 in the plasma membrane had a median survival of 30.2 months, whereas those expressing ZNF185 in the plasma membrane had a median survival of 21.3 months. A multivariate analysis indicated that the expression of ZNF185 in the plasma membrane was an independent poor prognostic factor (p = 0.016). A multivariate analysis indicated that patients with cells expressing ZNF185 in the plasma membrane were more likely to develop hematogenous metastasis (p = 0.081). NOD/Shi-scid/IL-2Rγ null (NOG) mice were used to compare the expression of ZNF185 in the subcutaneous tumors of the parent cell line BxPC-3 and liver metastatic tumors of the highly liver-metastatic subline LM-BxPC-3 established in our laboratory. Cells expressing ZNF185 in the plasma membrane were more prevalent in metastatic disease in the liver than in subcutaneous tumors, and these cells were often located at the tumor margins rather than in the center of the tumor. In conclusion, ZNF185 is a protein related to hematogenous metastasis, the expression of which in the plasma membrane was identified as an independent prognostic factor for pancreatic cancer. Citation Format: Daisuke Furukawa, Tsuyoshi Chijiwa, Masahiro Matsuyama, Masaya Mukai, Ei-ichi Matsuo, Osamu Nishimura, Kenji Kawai, Hiroshi Suemizu, Toshio Nakagohri, Seiei Yasuda, Kazuaki Shimada, Nobuyoshi Hiroka, Masato Nakamura. Clinical significance of ZNF185 intracellular localization in pancreatic ductal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1543.