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骨桥蛋白与基质金属蛋白酶-9在胰腺癌中的表达及其临床意义

Expression and Clinical Significance of Osteopontin and Matrix Metalloproteinase-9 in Pancreatic Cancer

【作者】 李西梅

【导师】 杨少奇;

【作者基本信息】 宁夏医科大学 , 内科学, 2009, 硕士

【摘要】 目的(1)检测骨桥蛋白(osteopontin,OPN)与基质金属蛋白酶-9(matrix metallo- -proteinase-9,MMP-9)在胰腺癌组织中的表达,分析其与临床病理特征的关系。(2)探讨胰腺癌中OPN与MMP-9的相互关系及可能的作用机制。(3)评估血清OPN检测在胰腺癌早期诊断及预后判断中的价值。方法(1)免疫组织化学UltraSensitiveT SP法检测OPN与MMP-9在50例胰腺癌、30例癌旁组织中的表达。(2)ELISA法和电化学发光免疫分析法检测30例胰腺癌患者及20例健康志愿者的血清OPN、CA199、CEA水平。(3)ROC曲线法比较OPN、CA199、CEA诊断胰腺癌的敏感度和特异度,评估OPN在胰腺癌诊断中的价值。结果(1)OPN和MMP-9在胰腺癌组织中的阳性表达率(64.0%,62.0%)明显高于其在癌旁组织中的阳性表达率(20.0%,26.6%) (P<0.01)。(2)OPN和MMP-9的表达均与肿瘤的分化程度,TNM分期及淋巴结转移有关(P<0.05)。(3)胰腺癌组织中OPN与MMP-9的表达呈正相关(r=0.53,P<0.01)。(4)胰腺癌患者血清OPN、CA199、CEA的水平(79.2±42.1ng/ml,397.5±360.0U/ml,4.3±3.8ug/ml)高于健康志愿者的血清OPN、CA199、CEA的水平(31.2±25.6 ng/ml,37.0±26.2U/ml,2.3±2.7ug/ml)(P<0.01或0.05)。(5)联合检测血清OPN、CA199、CEA的诊断胰腺癌的敏感度(96.7%)高于单独检测任一指标的敏感度(56.7%,86.6%,36.4%)(P<0.05)。结论(1)OPN与MMP-9在胰腺癌组织中均呈高表达,其表达与肿瘤的侵袭转移密切相关。(2)胰腺癌组织中OPN与MMP-9的表达呈正相关,两者在胰腺癌发生发展中可能起协同作用。(3)胰腺癌患者血清OPN水平与肿瘤分期及远处转移有关,可作为临床评估病情,监测疗效、判断预后的重要指标。(4)联合检测血清OPN、CA199与CEA水平有助于提高胰腺癌的诊断率,对于胰腺癌筛查有重要意义。

【Abstract】 Objective ( 1 ) To detect the expression of osteopontin (OPN) and matrix metalloproteinase-9(MMP-9) in pancreatic cancer tissue, and analyse its relationship with clinicopathological characteristics.(2) To explore the correlation between OPN and MMP-9 of pancreatic cancer and their possible mechanism of operation.(3) To evaluate the value of OPN in the early diagnosis and the prognosis assessment of pancreatic cancer.Methods(1)Immunohistochemical UltraSensitiveT SP method was used to detect the expression of OPN and MMP-9 in 50 cases of pancreatic cancer tissues and 30 cases of tumor-adjacent tissues.(2)The Serum levels of OPN,CEA,CA199 in 30 patients with pancreatic cancer and 20 healthy volunteers were measured by enzyme-linked immunosorbent assay and electrical chemiluminescence immunoassay.(3)Receiver operating characteristics curve (ROC) was used to compare the diagnostic sensitivity and specificity of OPN, CEA, and CA199 in the patients with pancreatic cancer , The value of OPN in the diagnosis of pancreatic cancer was assessed.Results (1)The positive rates of OPN and MMP-9 (64.0%,62.0%)in Pancreatic cancer tissue was significantly higher than in tumor-adjacent tissues(20.0%,26.6%) (P<0.05)(.2)The expression of OPN and MMP-9 were correlated with tumor differentiation,TNM stage and lymph node metastases of pancreatic cancer (P< 0.05).(3)There was a positive correlation between the expression of OPN and MMP-9 in pancreatic cancer tissue (r=0.53,P<0.01). (4)The serum levels of OPN, CA199 and CEA in patients with pancreatic cancer(79.2±42.1 ng/ml,397.5±360.0U/ml,4.3±3.8ug/ml)were higher than in healthy subjects(31.2±25.6 ng/ml,37.0±26.2U/ml,2.3±2.7ug/ml)(P<0.01or 0.05).(5)The sensitivity of combined detection with serum OPN, CEA, or CA199(96.7%) was higher than respective detection of OPN, CEA, or CA199(56.7%,86.6%,36.4%) in diagnosis of pancreatic cancer.Conclusion(1)OPN and MMP-9 are highly expressed in Pancreatic cancer tissues. The expression of them is closely related to the invasion and metastases of pancreatic cancer.(2)The expression of OPN and MMP-9 is positive correlated and probably coordinated in the occurrence and development of pancreatic cancer(.3)The serum osteopontin is closely related to distant metastasis and TNM stages of the Pancreatic cancer.The serum OPN may be an important maker to assess the outcome of pancreatic cancer and to monitor the efficacy of clinical treatment, to determine prognosis.(4)Combined detection with serum OPN, CA199, CEA can improve the rate of diagnosis. It also has important significance for the screening of pancreatic cancer.

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