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

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• 作者：Qingying Zhang ; Min Zhu ; Wenxiang Cheng…
• 关键词：S100A14 ; Gastric cancer ; Differentiation ; Genetic variant ; Prognosis
• 刊名：Journal of Cancer Research and Clinical Oncology
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：141
• 期：4
• 页码：691-703
• 全文大小：2,431 KB
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• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Cancer Research
  Internal Medicine
  Hematology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-1335

文摘

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?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.