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Low expression of fibulin-1 correlates with unfavorable prognosis in gastric cancer

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Tumor Biology

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.

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Acknowledgements

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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    Authors and Affiliations

    1. Department of General Surgery, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China

      Liang Feng, Peng Li, Ying Feng, Fei Wang, Qin-Sheng Mao & Wan-Jiang Xue

    2. Department of Pathology, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China

      Chan Yao & Yi-Fei Liu

    3. Department of Surgical Comprehensive Laboratory, Nantong University Affiliated Hospital, Nantong, 226001, Jiangsu, China

      Yi-Bing Guo

    4. Department of Minimally Invasive Surgery, The Affiliated Hospital of Nantong University, 20 Xisi Street, Nantong, 226001, Jiangsu, China

      Qin-Sheng Mao & Wan-Jiang Xue

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    1. Liang Feng
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    Liang Feng and Chan Yao contributed equally to this work.

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    Feng, L., Yao, C., Li, P. et al. Low expression of fibulin-1 correlates with unfavorable prognosis in gastric cancer. Tumor Biol. 37, 9399–9410 (2016). https://doi.org/10.1007/s13277-015-4537-1

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