胃癌组织中S100P表达的临床意义及其机制探讨

Impact of S100P expression on clinical outcomes of gastric cancer patients with adjuvant chemotherapy of oxaliplatin and its mechanisms

目的 探讨胃癌肿瘤组织中S100P的表达水平对患者预后及肿瘤化疗敏感性的影响及其可能机制.方法 回顾性分析2003年1月至2007年12月连续收治的121例胃癌根治术（D2）并同时接受奥沙利铂为主的辅助化疗患者的临床病理资料.镜下选取患者病理HE染色切片中的胃癌组织3处,对应标本蜡块制作成组织芯片,并行S100P免疫组化染色.结合随访资料和临床病理特征进行统计学分析.构建pEGFP-S100P质粒,对BGC823胃癌细胞进行转染,经G-418筛选后建立SlOOP稳定表达的混合细胞克隆,以探讨S100P不同表达水平对胃癌细胞对奥沙利铂的化疗敏感性的影响.Real-time PCR及Western blot分别检测混合细胞克隆中S100P mRNA和蛋白表达水平以验证转染成功.MTT法检测S100P过表达细胞株对奥沙利铂的化疗敏感性.结果 免疫组化染色提示胃癌组织中S100P阳性率为52.9%（64/121）.S100P阳性组累积5年生存率（20.3%）明显高于阴性组（3.5%）（P=0.034）,但其表达水平与肿瘤分期、淋巴结转移、远处转移和分化程度等无相关性.S100P过表达的BGC823胃癌细胞中,S100P mRNA和蛋白水平均较对照组显著增高（8.42±1.38比0.83±0.11和3.52±0.48比0.97±0.19,P值均〈0.05）.MTT法提示奥沙利铂对S100P过表达组和对照组的半抑制浓度（IC50）分别为（142±16）ms/L和（266±11）ms/L（P=0.032）.结论 S100P可能是预测胃癌患者预后的新指标之一,提高胃癌细胞对奥沙利铂化疗的敏感性可能是其改善累积生存率的机制之一.

Objective To investigate the impact of the expression of S100P on the prognosis and tumor chemosensitivity in patients with resectable gastric cancer and its mechnisms. Methods The expression of S100P was analyzed in 121 resected primary gastric cancer tissues by using tissue array of immunohistochemistry excised from January 2003 to December 2007. The patients received adjuvant chemotherapy with oxaliplatin. The pEGFP-SlOOP plasmid was constructed and was transfected into BGC823 cell line to establish gastric cancer cell line with over-expression of human S100P, BGC823-S100P. The expression level of S100P was determined by real-time PCR and Western blot assay. The chemosensitivity of BGC823-S10OP cell line to oxaliplatin was detected by 3-（ 4, 5-Dimethylthiazol-2-yl ）-2, 5-diphenyltetrazolium （MTT） assay. Results The S100P was positively expressed in 64 tumors（52. 9% , 64/ 121）. Although there was no significant relation between the expression of S100P and tumor T staging（ P = 0. 683）, N staging（ P = 0. 472）, M staging （P = 0. 770 ） and differentiation （P = 0. 553）, Wilcoxon test showed that the 5-year cumulative survival rate of patients with positive S100P expression was significantly higher than that of patients with negative expression （20.3% vs. 3.5%, P =0.034）. Furthermore, overexpressed of S100P was found in the BGC823 cell line, BGC823-S100P. The mRNA and protein level of S1O0P in pEGFP transfected BGC823-S100P cell lines were significantly higher than those in control group （8.42±1.38 ra. 0.83±0.11 and 3. 52±0.48 vs. 0. 97±0. 19,all P 〈0. 05）. It indicated with MTT assay that the half-inhibitory concentration（IC50） to oxaliplatin decreased in BGC823-S1OOP cells, and was significantly lower than that in vector-only transfected cells[ （ 142±16） mg/L vs. （266± 11 ） mg/L,P = 0. 032]. Conclusions S100P may also be a potentially novel independent prognostic factor in gastric cancer patients following curative resection. And it could improve the cumulative survival of the patients through enhancing the chemosensitivity of tumor cell line to oxaliplatin.