Role of the Stemness Factors Sox2, Oct3/4, and Nanog in Gastric Carcinoma

Abstract

Cancer stem cells have been proposed to be responsible for cancer tumorigenicity, and then to persist in tumors as a distinct population and cause relapse and metastasis. Recently, the stemness factors Sox2, Oct3/4, and Nanog were associated with induced pluripotent stem cells, suggesting a correlation between these stemness factors and cancer stem cells. We therefore investigated the role of stemness factors in the tumorigenesis of human gastric cancer. A total of 290 patients who had undergone resection of a primary gastric cancer at our institute were enrolled. A curative R0 resection was performed for 253 of 290 patients, and the remaining 37 patients were treated with a palliative resection. The expression levels of Sox2, Oct3/4, and Nanog were analyzed by immunohistochemistry. Sox2, Oct3/4, and Nanog expression were positive in 159 (55%), 129 (44%), and 28 (10%) of 290 gastriccancers, respectively. There was a statistically significantcorrelation between Sox2-positive or Oct3/4-negative expression and invasion depth, lymph node metastasis, or lymphatic invasion. In 253 patients with a curative resection, the prognosis of patients with Sox2-positive tumors or Oct3/4-negative tumors was significantly (P < 0.01 or P = 0.04, log-rank) worse than that of patients with Sox2-negative or Oct3/4-positive tumors, respectively. A multivariate analysis revealed the expression of Sox2 or Oct3/4 tobe an independent prognostic factor (P = 0.01 or P = 0.04). Sox2-positive expression or Oct3/4-negative expression might be associated with invasion of gastric cancer. Sox2 and Oct3/4 might be independent prognostic factors for patients with gastric cancer.