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

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.

• Authors: Qingying Zhang, Min Zhu, Wenxiang Cheng, Rui Xing, Wenmei Li, Min Zhao, Liyan Xu, Enmin Li, Guangbin Luo, Youyong Lu
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 141 Issue 4 Pg. 691-703 (Apr 2015) ISSN: 1432-1335 [Electronic] Germany
• PMID: 25266115 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5' Untranslated Regions
• Calcium-Binding Proteins
• S100A14 protein, human

Topics

• 5' Untranslated Regions (genetics)
• Base Sequence
• Blotting, Western
• Calcium-Binding Proteins (genetics, metabolism)
• Cell Line, Tumor
• Down-Regulation
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prognosis
• Promoter Regions, Genetic (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Stomach Neoplasms (genetics, metabolism, pathology)