SOX9 expression and its methylation status in gastric cancer

Abstract

SOX9 is a member of the SOX [Sry-related high-mobility group (HMG) box] family and is required for the development and differentiation of multiple cell lineages. To clarify the significance of SOX9 in gastric carcinoma (GC), immunohistochemical expression of SOX9 and the CpG island methylation status of SOX9 were evaluated and compared with clinicopathological factors including overall survival. SOX9 expression was immunohistochemically evaluated in 382 GC tumors and the methylation status was examined in 121 GC tumors. SOX9 expression and its methylation status in six GC cell lines, their Epstein-Barr virus (EBV)-infected cell lines, and two EBV-associated GC cell lines was also examined. The SOX9 expression increased from non-neoplastic mucosa to early cancer. High expression of SOX9 was seen in 212 cases (56%). SOX9 expression was inversely related to advanced tumor stage, vessel infiltration, nodal metastasis, and EBV infection. Fifty-eight (48%) of 121 GC tumors had a methylated promoter in GC and the methylated status was related to low expression. The expression and methylation status were not related to prognosis. Three of six cell lines had increased methylation through EBV infection and decreased SOX9 expression. Upregulation of SOX9 is related to GC development. Downregulation by promoter methylation is related to GC progression and EBV infection. SOX9 is closely related to GC carcinogenesis and EBV-associated GC carcinogenesis.

Aberrant expression of SOX9 is associated with gastrokine 1 inactivation in gastric cancers

“…Basal expression patterns of SOX9 were similar in the corpus and pylorus, consistent with that of a Japanese study [12,13]. SOX9 overexpression was detected in 64 (34.6 %) of 185 gastric cancers (Fig.…”

“…In colon cancer [20,21] and breast cancer [22], SOX9 overexpression was correlated with cancer progression and a poor overall prognosis. In contrast, it has been reported that SOX9 is related to the development of gastric cancer, but it decreases through progression of gastric cancer [13]. Radulescu et al [23] have recently reported that the altered Wnt/b-catenin signaling pathway in the stomach epithelium rapidly generates an initiating step in gastric tumorigenesis.…”

“…Thus, our results further support that SOX9 overexpression by GKN1 inactivation may contribute to the development of gastric cancer as an early event. However, because GKN1 also plays a role in the progression of gastric cancer by regulating expression of E-cadherin and representative EMT markers including bcatenin, slug, snail, fibronectin [7], and SOX9 expression was decreased through progression of gastric cancer [13], further studies are strongly needed to clarify the regulatory mechanism of SOX9 by GKN1 in the progression of gastric cancer.…”

“…In human embryonic tissues at 7.5 weeks gestational age, epithelial SOX9 expression is detected in the small intestine and mesodermal SOX9 expression is detected in the posterior region of the stomach at the pyloric area [11]. Numerous studies have demonstrated that SOX9 is involved in carcinogenesis in several types of cancers, including gastric cancers [12,13].…”

Expression and Clinical Significance of SOX9 in Renal Cell Carcinoma, Bladder Cancer and Penile Cancer

“…SOX9 belongs to the SOX (SRY (sex-determining region Y) box) gene superfamily, and is a key regulator of developmental processes, including male sex determination, chondrogenesis, neurogenesis, and neural crest development [4]. Additionally, SOX9 is a transcription factor and a downstream target gene of the Wnt/β-catenin signaling pathway [5,6], which is closely related to the emergence and development of tumor [7,8], and regulation of intestinal epithelial homeostasis [5,6].…”