MON-313 High Expression of Nucleobindin-2 Is Associated with Poor Prognosis in Gastric Cancer

Abstract

Nucleobindin-2 (NUCB2) is a 396-amino acid protein, cleaved into the N-terminal nesfatin-11-82, nesfatin-285-163and the C-terminal nesfatin-3166-396. NUCB2 contains a signal peptide, a leucine zipper structure, two Ca2+binding EF-hand domains, and has a wide variety of basic cellular functions. NUCB2 is also a precursor protein of nesfatin-1, which was originally identified in hypothalamic nuclei, and which is a regulatory factor involved in the central control of food intake and energy balance. There are several reports indicating that NUCB2 is also expressed in various human peripheral tissues. Moreover, recent studies have reported that high levels of NUCB2 mRNA and protein are a potent prognostic factor for prostate cancer, endometrial carcinoma, and breast cancer. Suzuki et al.described high NUCB2 immunoreactivity in patients with breast cancer, and NUCB2 protein expression associated significantly with lymph node metastasis and an increased risk of recurrence. They found that NUCB2 significantly increased tumor cell proliferation, migration, and invasion, suggesting that NUCB2 plays a crucial role in the metastatic process of breast cancer. Several researchers have reported that the expression level of NUCB2 was significantly higher in prostate cancer tissues than in non-cancerous tissues, and was associated with lymph node metastasis and shorter survival. However,theclinicopathologicalsignificance of NUCB2 expression in gastric cancer has still not beenelucidated. Therefore, we examined NUCB2 expression in a large number of gastric cancer patients, using immunohistochemistry, to explore its clinicopathologicalsignificance. To explore this, we aimed to investigate the NUCB2 expression in gastric cancer tissues and adjacent non-tumor tissues and its potential relevance to clinicopathological factors and prognosis using immunohistochemistry analysis. In our study, NUCB2 level in gastric cancertissues was higher than in non-tumor tissues. A high expression of NUCB2 is significantly associated with tumor depth, lymph node metastasis, lymphatic invasion, venous invasion and clinical stage. Furthermore, the expression level of NUCB2 protein was independent predictor of progression-free survival. In summary, NUCB2 might play a crucial role in gastric cancerdevelopment and could serve as an independent predictor of prognosis of gastric cancerpatients.