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Dig Dis Sci (2014) 59:21362144 DOI 10.1007/s10620-014-3137-z
ORIGINAL ARTICLE
S100A6 as a Potential Serum Prognostic Biomarker and Therapeutic Target in Gastric Cancer
Jianli Zhang Kejun Zhang Xiuli Jiang
Jian Zhang
Received: 31 December 2013 / Accepted: 23 March 2014 / Published online: 5 April 2014 Springer Science+Business Media New York 2014
AbstractBackground Increased expression of S100A6 in many cancer tissues and its association with tumor behavior and patient prognosis were demonstrated, and there are no studies analyzing the serum levels of S100A6 in patients with gastric cancer (GC).
Aim Serum S100A6 levels were investigated as a marker of tumor aggressiveness in patients with GC, and the S100A6 gene was examined as a potential therapeutic target in GC.
Methods Serum S100A6 levels were detected in 103 GC patients and 72 healthy subjects by ELISA. Clinicopatho-logical features of GC patients were analyzed in correlation to serum S100A6 levels. Two small interfering RNAs against S100A6 (siRNA1-S100A6 and siRNA2-S100A6) were generated and transfected into SGC7901 cells using pSUPER gfp-neo vector, and the effects of S100A6 knockdown on cell proliferation, invasion and apoptosis were evaluated in vitro. The effects of S100A6 silencing on tumor growth and metastasis were evaluated in vivo in a pseudo-metastatic GC nude mouse model.
Results Serum S100A6 levels were signicantly higher in GC patients than in healthy controls (P \ 0.001). Serum
S100A6 levels were signicantly correlated with lymph node metastasis, TNM stage, perineural invasion and vascular invasion. Serum S100A6 level was an independent
predictor of overall survival. SiRNA-mediated silencing of S100A6 signicantly induced apoptosis and decreased proliferation, clone formation and the invasiveness of GC SGC7901 cells in vitro and signicantly reduced tumor volume and number in vivo (P \ 0.01).
Conclusion Serum S100A6 level may serve as a potential prognostic biomarker in GC. Inhibition of S100A6 decreased the metastatic potential of GC cells.
Keywords Gastric cancer Biomarker Metastasis
S100A6
Introduction
Gastric cancer (GC) is the second leading cause of cancer-related death worldwide. It was predicted to be the eighth leading cause of death from all causes worldwide in the year 2010 [1, 2]. The prognosis of GC depends highly on the clinical and pathological stage at diagnosis. Surgical resection remains the mainstay of treatment and is very effective in early stage cancers. However, most...