Abstract 49: Zinc finger protein 185 is a key molecule of liver metastasis in colon cancer

Abstract

Abstract Colorectal cancer is among the three leading causes of cancer-related deaths worldwide. Nearly 50% of patients with colon cancer develop liver metastases. Mortality associated with the advanced stage of colon cancer has principally been attributed to the development of liver metastases. Therefore, clarifying the biological mechanisms underlying liver metastasis from colon cancer and accelerating the development of new treatment strategies are needed. We isolated Zinc finger protein 185 (ZNF185) as a metastasis-related protein by global quantitative proteome analysis of the in vivo liver metastasis model of super immunodeficient NOG mice with the highly liver-metastatic subline SW48-LM2 (Matsuo E, et al. AACR, #3947, 2008). LIM domain proteins have many fundamental biological processes including cell lineage specification, cytoskeleton organization, and organ development. ZNF185 is one of the LIM domain proteins and is considered to be involved in regulating cellular differentiation and/or proliferation. However, the functions and properties of ZNF185 in the multi-step process of cancer biology have not yet been elucidated in detail. In the present study, we analyzed the relationships between ZNF185 and the clinicopathological features of colon cancer (age, gender, histological type, lymphatic involvement, venous involvement, T and N statuses, liver metastasis, and stage). The expression of the ZNF185 protein was immunohistochemically analyzed. The expression of ZNF185 was detected in the cancer cells of 78 of 87 colon cancer patients. A correlation was observed between ZNF185 and the histological type (p=0.010, G-test). The expression of ZNF185 was also correlated with liver metastasis (p=0.030, G-test). Multivariate analysis using the Cox proportional hazards model was performed among the cause-specific survival rate, ZNF185 expression, and clinicopathological features. The histological type, liver metastasis, and ZNF185 expression were found to be independent prognostic indicators (p= 0.028, p<0.0001, p=0.036, respectively). ZNF185 expression was found to be an independent indicator of liver metastasis and prognosis in colon cancer. Citation Format: Daisuke Furukawa, Tsuyoshi Chijiwa, Masahiro Matsuyama, Masaya Mukai, Ei-ichi Matsuo, Osamu Nishimura, Kenji Kawai, Hiroshi Suemizu, Nobuyoshi Hiraoka, Toshio Nakagohri, Seiei Yasuda, Masato Nakamura. Zinc finger protein 185 is a key molecule of liver metastasis in colon cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 49. doi:10.1158/1538-7445.AM2014-49