Abstract 992: Significance of an autophagy protein, microtubule-associated protein light chain 3 (LC3), in gastric cancer

Abstract

Abstract Background: Autophagy is an intracellular degradation system that is induced under starvation or hypoxia. Recently, autophagy has been reported to be associated with carcinogenesis and tumor progression. The significance of autophagy in gastric cancer progression remains controversial. Microtubule-associated protein light chain 3 (LC3) is a component of autophagosomes that stimulate autophagy. There are 3 types of LC3 gene family members, LC3A, LC3B and LC3C. LC3A and LC3B were recently reported to be associated with autophagy in LC3 members. The aim of this study was to evaluate the significance of an autophagy protein, LC3, in gastric cancer. Materials and Methods: A diffuse-type gastric cancer cell line, OCUM-2MD3, was used in this study. Effect of starvation on the expression level of LC3A and LC3B mRNA of OCUM-2MD3 cells was examined by RT-PCR under glucose free condition. A total of 528 patients who underwent resection of a primary gastric cancer were enrolled. The correlation between the clinicopathological features of 528 primary gastric carcinomas and LC3 expression was examined by immunohistochemistry. Results: Expression level of LC3A and LC3B mRNA significantly increased five and two times respectively in OCUM-2MD3 under glucose free conditions compared to that under high glucose conditions. Immunohistochemical study showed that LC3 expression was positive in 94 (17.8%) of 528 gastric cancers. There was a statistically significant correlation between LC3 positive-expression and histologic type (p = 0.002), lymphatic invasion (p<0.001), venous invasion (p<0.001), and hepatic metastasis (p = 0.033). The Kaplan-Meier survival curve showed that LC3 expression was significantly associated with poor overall survival (p<0.001). Univariate analysis showed that LC3 expression was associated with poor prognosis in gastric cancer patients (p = 0.040), while multivariate analysis found that LC3 expression was not statistically significant (p = 0.255). Conclusion: LC3 might play an important role for autophagy of gastric cancer cells in starvation condition. LC3 is associated with progression of gastric cancer, and is a useful prognostic marker for patients with gastric cancer. Citation Format: Go Masuda, Masakazu Yashiro, Hiroaki Kasashima, Haruhito Kinoshita, Tatsunari Fukuoka, Tamami Morisaki, Tsuyoshi Hasegawa, Katsunobu Sakurai, Takahiro Toyokawa, Naoshi Kubo, Hiroaki Tanaka, Kazuya Muguruma, Masaichi Ohira, Kosei Chung. Significance of an autophagy protein, microtubule-associated protein light chain 3 (LC3), in gastric 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 992. doi:10.1158/1538-7445.AM2015-992