【作者】 贾富鑫；

【导师】 张东； 刘江伟；

【作者基本信息】 石河子大学 ， 外科学， 2011， 硕士

【摘要】 目的：通过检测钙离子结合蛋白S100A4、生存素(Survivin)及环氧化酶2(COX-2)在胰腺癌中的表达情况,探讨三者在胰腺癌中的表达与临床病理因素及预后的关系,进一步阐明S100A4在胰腺癌组织中的作用机制,为进一步应用干预S100A4活性的方法治疗胰腺癌提供实验依据。方法：①采用免疫组化二步法(PV法)检测63例手术切除的原发性胰腺导管腺癌组织及11例癌旁正常胰腺组织中S100A4、Survivin及COX-2的表达情况。②应用x2检验的统计学方法分析胰腺癌组织S100A4、Survivin及COX-2蛋白表达与临床病理因素的关系及对患者预后的影响;用Kaplan-Meier法分析生存曲线；多变量Cox北例风险回归模型筛选影响患者生存的独立预后因素。结果：①63例标本中S100A4和(?) Survivin及COX-2阳性率分别为74.6%(47/63),69.8%(44/63),73%(46/63)。②S100A4、Survivin蛋白过表达存在显著相关性(r=0.570,P=0.000);S100A4与COX-2蛋白过表达存在显著相关性(r=0.385,P=0.002)；Survivin与COX-2蛋白过表达也存在显著相关性(r=0.613,P=0.000)。③S100A4表达与肿瘤的TNM分期(P=0.002)、淋巴结转移(P=0.002)及远处转移(P=0.007)显著相关;Survivin表达与肿瘤的TNM分期(P=0.034)、淋巴结转移(P=0.020)及分化程度(P=0.000)显著相关；COX-2的表达与肿瘤大小(P=0.013)、分化程度(P=0.001)、TNM分期(P=0.021)、远处转移(P=0.031)及淋巴结转移(P=0.022)显著相关。④S100A4阴性/Survivin阴性组患者(11例)中位生存时间(大于36个月)明显大于S100A4阳性/SurvivinP日性组患者(37例)中位生存时间(9个月)(Log-rank检验,x2=17.754,P=0.000)；S100A4阴性/COX-2阴性组患者(8例)中位生存时间(大于36个月)明显大于S100A4阳性/COX-2阳性组患者(37例)中位生存时间(9个月)(Log-rank检验,x2=44.969, P=0.000); Survivin阴性/COX-2阴性组患者(9例)中位生存时间(大于36个月)也明显大于Survivin阳性/COX-2阳性组患者(38例)中位生存时间(9个月)(Log-rank检验,x2=34.128,P=0.000)。⑤分化程度(P=0.002)、TNM分期(P=0.002)、S100A4过表达(P=0.001)、Survivin过表达(P=0.024)及COX-2过表达P=0.002)是影响胰腺癌预后的独立因素。结论：S100A4、Survivin和COX-2的高表达与胰腺癌的临床病理参数密切相关,在胰腺癌的生长浸润过程中,三者可能协同抑制肿瘤细胞凋亡、促进肿瘤细胞增殖及血管生成的作用,其高表达提示患者预后不良,联合检测S100A4与Survivin和COX-2表达可预测胰腺癌发生转移的危险性及患者预后情况。胰腺癌组织细胞的抗凋亡、促进增殖及血管生成的作用与S100A4的表达有关,S100A4可能成为胰腺癌基因治疗的新靶点,这为进一步应用干预S100A4活性的方法治疗胰腺癌提供实验依据。更多还原

【Abstract】 Objective:To detect the expression of calcium-binding protein S100A4, Survivin and COX-2 in pancreatic carcinoma (PC) and their correlation with clinicopathological parameters and prognosis of pancreatic carcinoma patients, investigate the mechanism of action of protein S100A4 in PC, to provide academic and experimental evidence of the treatment of PC by the intervention of S100A4.Methods:①he expressions of S100A4, Survivin and COX-2 were examined in 63 surgical specimens of primary pancreatic carcinoma and 11 surgical specimens of non-pancreatic carcinoma with immunohistochemistry PV method.②The relationship between S100A4, Survivin, COX-2, clinicopathological parameters and prognosis of PC was analyzed by X2 test in 63 cases of PC. Kaplan-Meier and multivariate Cox proportional hazards regression model analysis were applied to compare the survival curves and screen the independent prognosis factors respectively.Results:①Forty-seven of 63(74.6%)specimens of PC were positive for S100A4, Forty-four of 63(69.8%)pancreatic carcinoma specimens showed positive expressions of Survivin and Forty-six of 63(73.0%)specimens of PC were positive for COX-2 according to immunohistochemistry detection.②he positive expressions of S100A4 and Survivin were significantly correlated with PC (r= 0.570, P=0.000), The correlation was significant between S100A4 and COX-2 in PC (r=0.385, P=0.002), The positive expressions of Survivin and COX-2 were also significantly correlated with PC (r=0.613, P=0.000).③he expressions of S100A4 significantly correlated with TNM stages (P=0.002), lymph node metastasis (P=0.002)and distant metastasis (P=0.007); The expression of Survivin had a significant correlation with TNM stages(P=0.034), lymph node metastasis (P=0.020)and differentiation(P=0.000); The expressions of COX-2 significantly correlated with turner size (P=0.013), differentiation (P=0.001), TNM stages (P=0.021), lymph node metastasis (P=0.022) and distant metastasis (P=0.031).④he median survival time(>36 months) of 11 patients with S100A4(-)/Survivin (-) was significantly longer than that of the 37 patients with S100A4(+)/Survivin(+) (9 months, x 2=17.754, P=0.000); The median survival time(>36 months) of 8 patients with S100A4(-)/COX-2 (-) was significantly longer than that of the 37 patients with S100A4(+)/COX-2(+) (9 months, x 2=44.969, P=0.000); The median survival time(>36 months) of 9 patients with Survivin (-)/COX-2 (-) was significantly longer than that of the 38 patients with S100A4(+)/COX-2(+)(9 months, x 2=34.128, P=0.000).⑤The differentiation(P=0.002), TNM stages (P=0.002), S100A4(+)Expression (P=0.001), Survivin (+) expression(P=0.024) and COX-2(+) Expression (P=0.002) were the independent prognostic factors for pancreatic cancer.Conclusion:This study indicated that the expression of S100A4, Survivin and COX-2 proteins were related with clinicopathological parameters of pancreatic cancer patients, S100A4 combined with Survivin and COX-2 could cooperatively inhibit the cells into apoptosis, promote the proliferation and angiogensis in the process of growth and invasion in pancreatic cancer, over-expressions of S100A4, Survivin and COX-2 proteins maybe predict the poor prognostic of pancreatic cancer patients, They may be the potential indicators of metastasis and prognosis in pancreatic cancer. S100A4 expression in PC tissiue is related with the inhibition of cells apoptosis, promotion of the proliferation and angiogensis, S100A4 may be a new target for the treatment of PC, to provide academic and experimental evidence of the treatment of PC by the intervention of S100A4.更多还原