Abstract 1578: Cohesin complex-related genes in colorectal cancer

Abstract

Abstract Backgrounds: One of the hallmarks of cancer is chromosomal instability and it leads to aneuploidy. Defective sister chromatid cohesion represents a major cause of chromosome instability in human cancers. Stromal antigen (STAG) encodes a subunit of the cohesin complex, which regulates cohesion and segregation of sister chromatids. STAG contains STAG1, STAG2 related to somatic division and STAG3 related to meiosis. We evaluated the relationship between STAG and colorectal cancer. Materials and methods: We examined STAG mRNA expression in tumor tissues by real-time qPCR. The samples were obtained from 172 colorectal cancer patients who underwent curative resection from November 2009 to December 2013 at the Osaka International Cancer Institute, Japan. STAG mRNA expression was evaluated by comparing with clinicopathological features and patients’ survival. Patients were classified into a high STAG expression and low STAG expression groups. Kaplan-Meier survival curves were evaluated using the log-rank test. The association with STAG expression and prognosis was analyzed by the Cox proportional regression model. Then, we utilized siRNA to knock down the expression of STAG3 and examined whether this altered proliferation in colorectal cancer cell lines (HCT116, RKO, HT29 and SW480). Results: STAG1 and STAG2 did not show no statistically significant differences in disease-free survival (DFS) and overall survival (OS). In contrast, DFS rate was significantly lower in the high STAG3 expression group than the low STAG3 expression group (P = 0.032). A multivariate analysis showed that the high STAG3 mRNA expression was a significant independent risk factor for the recurrence (P = 0.006). In patients with adjuvant chemotherapy, the high STAG3 expression group was significantly worse for DFS (P = 0.043) and OS (P = 0.020), compared to the low STAG3 expression group. However, the proliferation assays evaluating the knockdown of STAG3 did not show any significant differences. Conclusions: Our study showed that STAG3 can be a novel prognostic biomarker and the high STAG3 mRNA expression was an independent risk factor for the recurrence, suggesting that it relates to the chemotherapy resistance in colorectal cancer. We perform some other assays to evaluate the biology (focusing on the cancer invasiveness, the drug sensitivity, etc.) which reveal the mechanism of STAG3 in colorectal cancer. Citation Format: Masaru Sasaki, Norikatsu Miyoshi, Kazuhiro Saso, Shiki Fujino, Hidekazu Takahashi, Naotsugu Haraguchi, Chu Matsuda, Taishi Hata, Hirofumi Yamamoto, Tsunekazu Mizushima, Masaki Mori, Yuichiro Doki. Cohesin complex-related genes in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1578.