Abstract 3403: SIAH and SIAH-interacting proteins as potential prognostic and predictive biomarkers in pancreatic adenocarcinoma

Abstract

Abstract Introduction:   Seven-In-Absentia Homolog (SIAH), an E3 ubiquitin ligase, is an essential downstream component of the RAS signal transduction pathway. SIAH, is a member of a highly evolutionarily conserved family of RING finger E3 ubiquitin ligases. Our previous published work has shown that SIAH is an essential signaling “gatekeeper” in the oncogenic K-RAS signal transduction cascade and SIAH is a new, effective and logical anti-K-RAS drug target against pancreatic cancer. Our previous immunohistochemistry studies have shown SIAH is a tumor-specific biomarker and SIAH expression progressively increased as pancreatic tumors progress from PanINs to pancreatic adenocarcinoma (PDCA) at late stages. In this study, we expand our observations by comparing the expression patterns of SIAH and several newly identified SIAH-interacting proteins using the Mayo Clinic pancreatic cancer tissue microarrays (TMA) in hope to identify new vulnerability and novel prognostic biomarkers in pancreatic cancer. We hypothesize that SIAH and SIAH-interacting proteins may serve as useful biomarkers helping to assess effectiveness of the anticancer treatment, disease progress and predict clinical outcome and patient survival in the clinical settings. Methods: In this double blind controlled study two hundred pancreatic adenocarcinoma patients at different stages of disease progression who had underwent surgical resection at the Mayo Clinic, Rochester, Minnesota. Tissue microarrays were generated using de-identified patient tumor biospecimens. 12x distinct TMA sets (with ∼ 700 TMA cores) were stained with 13x antibodies corresponding to our newly identified SIAH-interacting proteins and the IHC staining was scored by the Mayo Clinic GI expert and pancreatic cancer pathologist. This resulted in approximately 9000 histological cores and slides that were then analyzed. The correlation with respect to SIAH and SIAH-interacting proteins as a new prognostic and predictive biomarker were scored and analyzed using Excel and standard biostatistical softwares. Results: This study is performed in a double blind control settings and we are currently awaiting the disclosure of the clinical information from the pathologist for the final evaluation of SIAH and SIAH-interacting proteins with respect to disease progression, outcome and survival. Here we report the promising interactions have been observed between SIAH and several putative biomarkers in pancreatic cancer. Conclusion: As we previously reported, SIAH/SIAH-interacting proteins may serve as useful prognostic biomarkers to predict cancer disease progression and patient survival in clinical settings. At the end of this study, we hope to establish and validate the prognostic value of the SIAH-complex as new biomarkers and a reliable readout for oncogenic K-RAS activation, pancreatic cancer cell dissemination and metastasis. Citation Format: Elizaevta Svyatova. SIAH and SIAH-interacting proteins as potential prognostic and predictive biomarkers in pancreatic adenocarcinoma. [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 3403. doi:10.1158/1538-7445.AM2015-3403