Abstract 143: A long non-coding RNA activated by TGF-β can predict the prognosis of gastric cancer patients
Authors: Tomoko Saito, Junji Kurashige, Sho Nambara, Hisateru Komatsu, Hidenari Hirata, Masami Ueda, Shotaro Sakimura, Ryutaro Uchi, Yuki Takano, Yoshiaki Shinden, Tomohiro Iguchi, Hidetoshi Eguchi, Keishi Sugimachi, Kazunari Murakami, Koshi Mimori
Journal: Cancer Research (2015)

Abstract Background: Long non-coding RNA (lncRNA) is known to play important roles in proliferation or metastasis in several human cancers. A recent study reported that lncRNA activated by TGF-β (lncRNA-ATB) induced Epithelial-Mesenchymal Transition (EMT) through the TGF-β/miR-200s/ZEB axis in hepatocellular carcinoma (HCC), therefore the high lncRNA-ATB patients in HCC had poor prognosis. EMT through the TGF-β/miR-200s/ZEB axis reported to be involved in invasion, metastasis, or dessemination in gastric cancer. Therefore, we focused on the clinical significance of lncRNA-ATB expression in gastric cancer. Materials and Methods: qRT-PCR was performed to examine expression of lncRNA-ATB, miR-200b, and miR-200c in gastric cancer tissues (n = 183). Then we divided patients into high and low lncRNA-ATB expression groups using lncRNA-ATB/GAPDH ≥0.55 or &amp;lt;0.55 to determine the clinicopathological significance of lncRNA-ATB in gastric cancer. Moreover we evaluated expressions of lncRNA-ATB, miR-200s and ZEB1 in gastric cancer cell lines by qRT-PCR. Gastric cancer cell lines with low lncRNA-ATB expression were treated by recombinant TGF-β1 to examine morphologic changes and genetic alterations, such as lncRNA-ATB, miR-200s, and ZEB1 levels, with respect to the EMT phenotype. Results: LncRNA-ATB expression levels in gastric cancer patients weren't associated with the clinicopathological factors, gender, age, tumor size, histological type, depth of tumor invasion, lymph node metastasis, lymphatic invasion, vascular invasion, liver metastasis, peritoneal dissemination, or distant metastasis. However, the high lncRNA-ATB group experienced a lower 5-year survival rate compared to the low lncRNA-ATB group (P = 0.003), and multivariate analysis indicated that lncRNA-ATB was an independent prognostic factor (HR = 3.18; 95%CI: 1.47-7.29; P = 0.0031). The lncRNA-ATB level was inversely associated with miR-200s in gastric cancer cell lines. The inverse association was validated in miR-200c and lncRNA-ATB in gastric cancer patients. Moreover, lncRNA-ATB and ZEB1 levels increased and miR-200c levels reduced in low lncRNA-ATB cells treated with TGF-β1 after 10 d of treatment. Morphologies also changed from epithelial to mesenchymal form. Conclusions: LncRNA-ATB plays an important role in EMT to promote invasion and metastasis through the TGF-β/miR-200s/ZEB axis, resulting in a poor prognosis in gastric cancer. Further investigations will demonstrate the significance of lncRNA-ATB as a novel lncRNA biomarker indicative of a poor prognosis in gastric cancer patients. Citation Format: Tomoko Saito, Junji Kurashige, Sho Nambara, Hisateru Komatsu, Hidenari Hirata, Masami Ueda, Shotaro Sakimura, Ryutaro Uchi, Yuki Takano, Yoshiaki Shinden, Tomohiro Iguchi, Hidetoshi Eguchi, Keishi Sugimachi, Kazunari Murakami, Koshi Mimori. A long non-coding RNA activated by TGF-β can predict the prognosis of gastric cancer patients. [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 143. doi:10.1158/1538-7445.AM2015-143