title: Aberrant methylation of the SPARC gene promoter and its clinical implication in gastric cancer.
abstract: Secreted protein acidic and rich in cysteine (SPARC) gene has been shown to be epigenetically silenced in several cancers. We investigated the loss of expression and promoter methylation of this tumor suppressor gene in gastric cancers and correlated the data with clinicopathological features. We observed the loss of SPARC mRNA and SPARC protein expression in 7 of 10 (70%) gastric cancer cell lines. Upon treatment of expression-negative cell lines with a demethylating agent, expression of mRNA and protein was restored in all cells. Methylation rate of SPARC gene was 80% in ten gastric cancer cell lines and 74% (163 of 220) in primary tumors, while it was 5% in normal gastric mucosa (n = 40). In intestinal gastric cancer, SPARC methylation correlated with a negative prognosis (P < 0.001; relative risk 2.754, 95% confidence interval 1.780-4.261). Immunostaining revealed that SPARC protein was overexpressed in stromal fibroblasts adjacent to neoplastic epithelium but rarely expressed in the primary gastric cancer cells. These results implicate SPARC promoter methylation as an important factor in the tumorigenesis of gastric carcinomas and provide new insights into the potential use of SPARC as a novel biomarker and the potential clinical importance in human gastric cancers.
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Zi-Yi
authors.initials: ZY
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Yao
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Peng-Yuan
authors.initials: PY
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Yuan-Lian
authors.initials: YL
authors.lastname: Wan
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Shan-Wen
authors.initials: SW
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Guo-Wei
authors.initials: GW
authors.lastname: Chen
authors.affiliation: Department of General Surgery, Peking University First Hospital, Beijing 100034, P.R. China.
authors.forename: Yu-Cun
authors.initials: YC
authors.lastname: Liu
mesh_terms: D063646:Carcinogenesis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D004848:Epithelium / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology; D005753:Gastric Mucosa / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D015676:Osteonectin / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D015676:Osteonectin; D012333:RNA, Messenger; C577241:SPARC protein, human