Abstract
Abstract Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family, which function as important regulators for carcinogenesis. In this study, we tested whether TRIM44 (11p13) acts as a cancer-promoting gene through overexpression in gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC). We analyzed 7 GC and 14 ESCC cell lines for in vitro analysis. We also analyzed 113 GC and 68 ESCC primary tumors, which were curatively resected in our hospital between 1998 and 2008. As the results, expression of the TRIM44 protein was detected in GC and ESCC cell lines (2/7 cell lines; 29% and 8/14; 57%, respectively) and primary tumor samples of GC and ESCC (24/113 cases; 24% and 39/68; 57%, respectively). Knockdown of TRIM44 expression using several specific siRNAs inhibited cell proliferation and migration and invasion in TRIM44-overexpressing GC cell, and inhibited cell migration and invasion in TRIM44-overexpressing ESCC. Using immunohistochemical analysis, overexpression of the TRIM44 was significantly correlated with an advanced type of macroscopic appearance, lymphatic invasion, and higher recurrence rate in GC, and with the status of the lymph node metastasis in ESCC. TRIM44-overexpressing tumors had a worse overall rate of survival than those with non-expressing tumors in GC and ESCC tumors. Moreover, TRIM44 positivity was independently associated with worse outcome in multivariate analysis in GC tumors. These findings suggest that TRIM44 plays a crucial role in tumor progress through its overexpression, and highlight its usefulness as a novel predictor and potential therapeutic target in GC and ESCC. Citation Format: Tsutomu Kawaguchi. Overexpression of TRIM44 contributes to malignant outcome in upper GI tract cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3425. doi:10.1158/1538-7445.AM2015-3425
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