Department of General Surgery, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Qingdao, 266509, Shandong, China,
Dig Dis Sci. 2014 Sep;59(9):2136-44. doi: 10.1007/s10620-014-3137-z. Epub 2014 Apr 5.
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).
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.
Serum S100A6 levels were detected in 103 GC patients and 72 healthy subjects by ELISA. Clinicopathological 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.
Serum S100A6 levels were significantly higher in GC patients than in healthy controls (P < 0.001). Serum S100A6 levels were significantly 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 significantly induced apoptosis and decreased proliferation, clone formation and the invasiveness of GC SGC7901 cells in vitro and significantly reduced tumor volume and number in vivo (P < 0.01).
Serum S100A6 level may serve as a potential prognostic biomarker in GC. Inhibition of S100A6 decreased the metastatic potential of GC cells.
在许多癌症组织中 S100A6 的表达增加，并与肿瘤行为和患者预后相关，但是目前还没有研究分析胃癌（GC）患者的血清 S100A6 水平。
研究血清 S100A6 水平作为 GC 患者肿瘤侵袭性的标志物，并探讨 S100A6 基因作为 GC 的潜在治疗靶点。
采用 ELISA 法检测 103 例 GC 患者和 72 例健康对照者的血清 S100A6 水平，分析 GC 患者的临床病理特征与血清 S100A6 水平的相关性。设计并合成 2 条针对 S100A6 的小干扰 RNA（siRNA1-S100A6 和 siRNA2-S100A6），转染至 SGC7901 细胞，通过 pSUPER gfp-neo 载体进行转染，体外观察 S100A6 敲低对细胞增殖、侵袭和凋亡的影响。在伪转移性 GC 裸鼠模型中体内观察 S100A6 沉默对肿瘤生长和转移的影响。
GC 患者的血清 S100A6 水平明显高于健康对照组（P<0.001）。血清 S100A6 水平与淋巴结转移、TNM 分期、神经周围侵犯和血管侵犯显著相关。血清 S100A6 水平是总生存的独立预测因子。S100A6 的 siRNA 介导的沉默显著诱导 GC SGC7901 细胞凋亡，降低增殖、克隆形成和侵袭能力，体内显著降低肿瘤体积和数量（P<0.01）。
血清 S100A6 水平可能是 GC 的潜在预后生物标志物。抑制 S100A6 降低了 GC 细胞的转移潜能。
