Abstract
Abstract Gastric cancer still ranks among the top ten most common cancer in the world, despite a declining trend in incidence. The multifunctional protein Y Box Binding Protein-1 (YB-1) is known to regulate transcription, translation, DNA repair and cellular response to drug treatment. This study evaluated the correlation between YB-1 protein expression levels with clinico-pathological characteristics in the intestinal type of gastric cancer, which was further validated with in vitro experimentation. Tissue microarrays (TMAs) were constructed from specimens obtained from 167 patients diagnosed with intestinal gastric cancer. Immunohistochemical analysis of the YB-1 protein was performed on the TMAs . The intensity of YB-1 staining in the intestinal type of gastric cancer was scored as absent to strong staining and the percentage of YB-1 immunostained cells was determined. YB-1 immunoreactivity was based on the weighted average intensity (WAI) for each specimen, which was calculated as the sum of percentages of stained cells for each intensity divided by the total percentage of stained cells. siRNA-mediated silencing of the YB-1 gene in MKN7 intestinal gastric cancer cells was verified by RT-PCR. Cell migration and invasion assays were carried out using commercially available kits. YB-1 immunostaining was present in all the cancer tissue samples examined. The YB-1 protein was observed to be predominantly expressed in the cytoplasm of the gastric cancer cells. Univariate analysis revealed that YB-1 immunohistochemical expression was significantly correlated with lymph node status and perforation. However, multivariate analysis showed that only YB-1 protein expression is an independent predictor of lymph node spread. Down-regulation of the YB-1 gene expression in MKN7 cells significantly inhibited cell migration and invasion, processes which are important in the metastatic cascade. The findings suggest that YB-1 expression is associated with metastasis in the intestinal type of gastric cancer and is a potential prognostic biomarker and therapeutic target in this subtype of gastric cancer. Citation Format: TianTian Guo, Yingnan Yu, George Wai-Cheong Yip, Gyeong Hun Baeg, Aye Aye Thike, Puay-Hoon Tan, Ken Matsumoto, Boon Huat Bay. Y-box binding protein 1 is correlated with lymph node metastasis in intestinal type of gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 47. doi:10.1158/1538-7445.AM2014-47
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