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Downregulation of 425G>A variant of calcium-binding protein S100A14 associated with poor differentiation and prognosis in gastric cancer

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Altered level of S100 calcium-binding proteins is involved in tumor development and progression. However, their role in gastric cancer (GC) is not well documented. We investigated the expression pattern of S100 proteins and differentiation or prognosis as well as possible mechanisms in GC.

Methods

RT-PCR, Western blot analysis, and immunohistochemistry were used to determine the mRNA and protein expression of S100 family genes in GC. The polymorphisms of promoter and 5′-UTR of S100A14 gene were identified and related to luciferase reporter gene activity. Association of S100A14 expression with clinicopathologic features and survival in GC was analyzed.

Results

We detected upregulated S100A2, S100A6, S100A10, and S100A11 expression and downregulated S100P and S100B expression in GC. Particularly, we detected differential mRNA and protein expression of S100A14 in GC cell lines and primary tumors. Furthermore, S100A14 expression change was related to a differentiated GC phenotype, with an expression in 31/40 (77.5 %) samples of well-differentiated tumors and 29/85 (34.1 %) samples of poorly differentiated tumors (P < 0.001). Moreover, 5-year survival was better in GC cases with positive than negative S100A14 level (P = 0.02). The genetic variant 425G>A on the 5′-UTR of S100A14 was associated with reduced S100A14 expression in GC cells.

Conclusion

Decreased expression of S100A14 with presence of its genetic variant 425G>A may be associated with an undifferentiated phenotype and poor prognosis in GC.

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Acknowledgments

This study was supported by a grant from the State Key Basic Research Program (no. 2004 CB518708) and the National Bio-Tech 86-3 program (nos. 2001AA233061, 2002-BA711A11, and 2012AA02A203).

Conflict of interest

The authors have no potential conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Preventive Medicine, Shantou University Medical College, Shantou, 515041, Guangdong Province, China

    Qingying Zhang, Min Zhu & Wenxiang Cheng

  2. Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute, Beijing, 100142, China

    Rui Xing, Wenmei Li, Min Zhao & Youyong Lu

  3. Department of Chemistry, Shantou University Medical College, Shantou, 515041, Guangdong Province, China

    Liyan Xu & Enmin Li

  4. Department of Genetics Ireland Cancer Center, Case University, BRB 7th Flr. West, 10900 Euclid Avenue, Cleveland, OH, 44106-4919, USA

    Guangbin Luo

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  1. Qingying Zhang
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Correspondence to Youyong Lu.

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Zhang, Q., Zhu, M., Cheng, W. et al. Downregulation of 425G>A variant of calcium-binding protein S100A14 associated with poor differentiation and prognosis in gastric cancer. J Cancer Res Clin Oncol 141, 691–703 (2015). https://doi.org/10.1007/s00432-014-1830-0

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