鞘氨醇激酶1在胃癌组织中的表达及其与肿瘤浸润转移及预后的关系

目的 探讨鞘氨醇激酶1 (SPHK1)在胃癌组织中的表达及其与胃癌浸润、转移及预后的关系.方法 应用免疫组织化学SP法,检测浙江省人民医院2001年1月至2005年12月206例石蜡固定的胃癌组织和同期的40例非肿瘤胃黏膜中SPHK1的表达.结果 在40例非肿瘤胃黏膜组织中,3例(7.5％) SPHK1蛋白为阳性表达,均为低表达.在206例胃癌组织中,181例(87.9％)SPHK1蛋白阳性表达,明显高于非肿瘤胃黏膜组织(P =0.001),其中高表达126例(61.2％).SPHK1蛋白的表达与浸润深度、淋巴结转移、远处转移及TNM分期有关(P=0.039、0.003、0.020、0.003),而与患者性别、肿瘤部位、肿瘤大小、分化程度和组织学类型无关(均P＞0.05).Ⅰ～Ⅱ和Ⅲ期中SPHK1高表达胃癌患者5年生存率显著低于SPHK1低表达者53.6％( 15/28)比68.6％( 24/35),7.8％ (6/77)比30.8％(12/39),P=0.009、0.006],Ⅳ期胃癌患者的5年生存率与SPHK1表达无关(P＞0.05),多变量分析表明SPHK1表达、淋巴结转移、远处转移和TNM分期是胃癌患者独立的预后因素.结论 SPHK1的表达与胃癌淋巴结转移和远处转移及预后相关,SPHK1有望成为一个预测肿瘤预后的分子标志物.

Relationship between sphingosine kinase 1 expression and tumor invasion, metastasis and prognosis in gastric cancer

Objective To explore the clinical significance of sphingosine kinase 1 ( SPHK1 ) in the invasion,metastasis and prognosis of gastric cancer.Methods Immunohistochemistry was employed to analyze the expression of SPHK1 in 206 clinicopathologically characterized gastric cancer cases from January 2001 to December 2005 at Zhejiang Provincial People's Hospital.Results SPHK1 protein was detected in 3 (7.5％ ) of 40 human non-tumor mucosa.All samples expressed the protein at a low level.SPHK1 protein was detected in 181 (87.9％) of 206 human gastric cancer cases.An elevated expression of SPHK1 protein was detected in 126 (61.2％) tumors.And SPHK1 protein was up-regulated in gastric cancer lesions compared with adjacent noncancerous tissues( P =0.001 ).The expression of SPHK1 was correlated with the depth of invasion,lymph node metastasis,distant metastasis and TNM stage ( P =0.039,0.003,0.020,0.003).In stages Ⅰ - Ⅱ and Ⅲ,the 5-year survival rate of the patients with a high expression of SPHK1 was significantly lower than those with a low expression (53.6％ ( 15/28 )vs 68.6％ (24/35),7.8％ (6/ 77) vs 30.8％ ( 12/39 ),P =0.009,0.006).In stage ⅣV,the expression of SPHK1 was not correlated with the 5-year survival rate ( P ＞ 0.05 ).Further multivariate analysis suggested that lymph node metastasis,distant metastasis,TNM stage and the up-regulation of SPHK1 were independent prognostic indicators for gastric cancer.Conclusion The expression of SPHK1 in gastric cancer is significantly associated with lymph node metastasis,distant metastasis and a poor prognosis.SPHK1 may become a useful marker of predicting tumor progression and prognosis.