Abstract 4828: Differential gene expression profile of tissue factor pathway inhibitor-2 (TFPI-2) in malignant pleural mesothelioma

Abstract

Abstract Malignant pleural mesothelioma (MPM) is an asbestos-related malignancy characterized by rapid progressive local growth, late metastases, and poor prognosis despite aggressive strategies involving surgery, chemotherapy, and radiation. The tissue factor pathway inhibitor-2 (TFPI-2) has been shown to play an important role in the regulation of extracellular matrix digestion and remodeling, and its reduced synthesis is implicated in various pathophysiological processes such as inflammation and tumor growth/metastasis. In this study we have elucidated the gene expression profile of TFPI-2 among 22 MPM tumor samples using Affymetrix U133AB chip platform. We noticed 13/22 tumors had more than 3-fold reduction in their TFPI-2 gene expression patterns compared to three normal peritoneums. Decreased TFPI-2 expression was observed in majority of epithelial histotypes that exhibited short-term recurrence (STR <12 months) compared to longer time to relapse (LTR after surgery), group of MPM tumor samples. TFPI-2 expression was profoundly decreased (>4-fold) among 5 out of 7 autologous normal pleura-MPM tumor samples. We also found > 3-fold decreased TFPI-2 gene expression pattern in three out of six MPM patient derived cell lines. A robust 2-fold induction in TFPI-2 gene expression was found as a consequence of 5′-aza-2′-deoxycytidine (5-AzaC) and trichostatin-A combination treatment of two MPM patient derived cell lines. Studies are underway to assess whether TFPI-2 promoter hypermethylation is involved in the down-regulation of its expression pattern seen among fifty percent of MPM tumor samples. Further studies are needed to understand the regulation and interaction of TFPI-2 in mesothelioma carcinogenesis that could be utilized for future early detection and therapeutic strategies to combat this insidious disease. Note: This abstract was not presented at the meeting. Citation Format: Anil Wali, Ying Wang, Adi Tarca, Fulvio Lonardo, Zhandong Liu, Arun K. Rishi, Harvey I. Pass. Differential gene expression profile of tissue factor pathway inhibitor-2 (TFPI-2) in malignant pleural mesothelioma. [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 4828. doi:10.1158/1538-7445.AM2015-4828