title: 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.
authors.affiliation: Department of Pathology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Minhua
authors.initials: M
authors.lastname: Sun
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uozaki
authors.forename: Rumi
authors.initials: R
authors.lastname: Hino
authors.forename: Akiko
authors.initials: A
authors.lastname: Kunita
authors.forename: Aya
authors.initials: A
authors.lastname: Shinozaki
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ushiku
authors.forename: Takashi
authors.initials: T
authors.lastname: Hibiya
authors.forename: Kimiko
authors.initials: K
authors.lastname: Takeshita
authors.forename: Maya
authors.initials: M
authors.lastname: Isogai
authors.forename: Kenzo
authors.initials: K
authors.lastname: Takada
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D020031:Epstein-Barr Virus Infections / Q000150:complications; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055758:SOX9 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000821:virology; D046888:Tissue Array Analysis
chemical_list: D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human