Low expression of fibulin-1 correlates with unfavorable prognosis in gastric cancer
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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.
KeywordsFibulin-1 Gastric carcinogenesis Epigenetic Tumor suppressor gene Prognosis
This work was supported by the National Natural Science Foundation of China (no. 81000984), the Six Talent Peaks Project of the Jiangsu Province (2011-WS066), and the Social Undertakings of Science and Technology Innovation and Demonstration Project of Nantong City (HS2014042).
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- 8.Tsuburaya A, Mizusawa J, Tanaka Y, Fukushima N, Nashimoto A, Sasako M, et al. Neoadjuvant chemotherapy with s-1 and cisplatin followed by d2 gastrectomy with para-aortic lymph node dissection for gastric cancer with extensive lymph node metastasis. Br J Surg. 2014;101:653–60.CrossRefPubMedGoogle Scholar
- 35.Feil R, Fraga MF. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 2011;13:97–109.Google Scholar
- 36.Konturek PC, Konturek SJ, Brzozowski T. Gastric cancer and Helicobacter pylori infection. J Physiol Pharmacol. 2006;57 Suppl 3:51–65.Google Scholar