Abstract 450: Smad interacting protein 1 (SIP1) is associated with peritoneal carcinomatosis in intestinal type gastric cancer

Abstract

Abstract Purpose. Smad interacting protein 1 (SIP1) encodes a transcription factor and is one of the epithelial-mesenchymal transition (EMT)-inducible genes that play a key role in tumor progression in various cancers. The aim of this study is to clarify the clinical significance of SIP1 expression in gastric cancer patients, and to clarify its biological function especially in intestinal type gastric cancer. Methods. We studied one hundred thirty-four patients undergoing surgery for gastric cancer. We analyzed SIP1 mRNA levels by real-time reverse transcription PCR in gastric cancer tissue and adjacent normal mucosa, and in gastric cancer cell lines. SIP1 protein expression in primary cancer and in peritoneal dissemination samples was measured using immunohistochemical analysis. Knockdown of the SIP1 gene by siRNA transfection was performed to evaluate SIP1 function in gastric cancer cell. Results. Expression of the SIP1 gene was significantly higher in cancerous tissue than in adjacent normal mucosa (p<0.05). Increased SIP1 expression was significantly associated with peritoneal dissemination (p<0.05), and was an independent prognostic factor (risk ratio, 2.17; 95% confidence interval, 1.26-3.74; p<0.05). Logistic regression analysis revealed that increased SIP1 expression was an independent risk factor for peritoneal dissemination (odds ratio, 3.43; 95% confidence interval, 1.25-9.43; p<0.05). Especially in intestinal type gastric cancer, elevated SIP1 expression was significantly correlated with peritoneal dissemination and poor prognosis (p<0.05). Immunohistochemical analysis indicated that SIP1 was intensely expressed in both primary cancer and peritoneal dissemination samples. In vitro, cell proliferation, migration and invasion were inhibited by SIP1 knockdown, while resistance to anoikis was decreased after knockdown of SIP1 in the intestinal type gastric cancer cell line MKN7. Conclusion: High SIP1 expression is associated with poor prognosis especially in intestinal type gastric cancer patients and enhanced malignant potential in terms of proliferation, migration, invasion and anoikis inhibition in intestinal type gastric cacner cell. These results indicate that SIP1 plays an important role in progression to peritoneal carcinomatosis in intestinal type gastric cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 450. doi:1538-7445.AM2012-450