title: Low expression of fibulin-1 correlates with unfavorable prognosis in gastric cancer.
abstract: The tumor-suppressing role of fibulin-1 has been described in several types of cancers. However, the expression and role of fibulin-1 in the development and progression of gastric cancer (GC) remain largely unknown. In this study, RT-PCR and immunochemistry were used to detect the fibulin-1 expression in GC samples. We have found that the fibulin-1 protein and mRNA levels were downregulated in GC. When investigating the correlation between fibulin-1 expression and clinicopathological characteristics, we have found that low fibulin-1 protein expression was associated with poor tumor differentiation and advanced N stage. Low fibulin-1 protein expression was also an independent prognostic factor for patient survival. To clarify the reason of fibulin-1 downregulation in GC, the mRNA expression and methylation status of fibulin-1 were examined in GC fresh tissue samples (n = 36). We found that the transcriptional expression of fibulin-1 was negatively associated with fibulin-1 promoter hypermethylation, and fibulin-1 hypermethylation was associated with Helicobacter pylori infection. Finally, the effects of fibulin-1 overexpression on cell proliferation and apoptosis were examined. We have found that fibulin-1 overexpression suppressed the growth of GC both in vitro and in vivo and induced apoptosis by increasing cleaved caspase-3 expression. In conclusion, fibulin-1 acts as a tumor suppressor gene, is frequently hypermethylated in GC, and can potentially serve as a useful biomarker for patient prognosis.
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Feng
authors.affiliation: Department of Pathology, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China.
authors.forename: Chan
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pathology, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Liu
authors.affiliation: Department of Surgical Comprehensive Laboratory, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China.
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Guo
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China. maoqsh@sina.com.|Department of Minimally Invasive Surgery, The Affiliated Hospital of Nantong University, 20 Xisi Street, Nantong, 226001, Jiangsu, China. maoqsh@sina.com.
authors.forename: Qin-Sheng
authors.initials: QS
authors.lastname: Mao
authors.affiliation: Department of General Surgery, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China. 377209255@qq.com.|Department of Minimally Invasive Surgery, The Affiliated Hospital of Nantong University, 20 Xisi Street, Nantong, 226001, Jiangsu, China. 377209255@qq.com.
authors.forename: Wan-Jiang
authors.initials: WJ
authors.lastname: Xue
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D019175:DNA Methylation; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; C060820:fibulin
keywords: Epigenetic; Fibulin-1; Gastric carcinogenesis; Prognosis; Tumor suppressor gene