Supplementary Material for: Significance of the Lysyl Oxidase Members Lysyl Oxidase Like 1, 3, and 4 in Gastric Cancer

<b><i>Background/Aims:</i></b> Lysyl oxidase (LOX) family members play a key role in modifying the primary tumor microenvironment by crosslinking collagens and elastin in the extracellular matrix. The aim of this study was to analyze the LOX-like (LOXL)1, LOXL3, and LOXL4 expressions in gastric cancer tissue by immunohistochemical staining. <b><i>Methods:</i></b> The correlations between the clinicopathological features of 597 primary gastric carcinomas and LOX family members – LOXL1, LOXL3, and LOXL4 – were investigated by immunohistochemical studies. The effect of the transforming growth ­factor β1 (TGFβ1) on the expressions of <i>LOXL1, LOXL3,</i> and <i>LOXL4</i> in gastric cancer was examined using diffuse-type gastric cancer cell lines in vitro. <b><i>Results:</i></b> The expressions of LOXL1, LOXL3, and LOXL4 were correlated with T invasion, lymph node metastasis, and lymphatic and venous invasion. LOXL1 expression was associated with histological intestinal-type and expanding growth patterns. The overall survival of patients with LOXL1-, LOXL3-, or LOXL4-positive cancer was poorer than those with negative cancer. <i>LOXL3</i> and <i>LOXL4</i> mRNA expressions were significantly high in diffuse-type gastric cancer cells with high invasion ability. TGFβ decreased the LOXL1 expression and increased LOXL3 and LOXL4 expression. <b><i>Conclusion:</i></b> LOXL1, LOXL3, and LOXL4 expressions are associated with distant metastasis of gastric cancer.