乙酰肝素酶和MMP-9 在胰腺癌中的表达及临床意义*

Expression and Significance of Heparanase and MMP-9 in Pancreatic Carcinoma

  • 摘要: 目的:检测乙酰肝素酶(heparanase,HPA )和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)在胰腺癌、慢性胰腺炎、正常胰腺组织中的表达及相互关系,分析其与浸润转移的关系。方法:应用免疫组化SP法检测92例胰腺癌、24例慢性胰腺炎和10例正常胰腺组织中HPA 、MMP-9 的表达水平,分析两者的表达与临床病理指标的关系,建立Spearman 等级相关分析。结果:HPA 在胰腺癌中表达明显高于慢性胰腺炎和正常胰腺组织(P<0.05),HPA 阳性表达与周围组织浸润、淋巴结转移呈正相关(P<0.05),与性别、年龄及组织学分级无统计学相关(P>0.05);胰腺癌组织中MMP-9 表达明显高于慢性胰腺炎和正常胰腺组织(P<0.05),且MMP-9 阳性表达与周围组织浸润、远处转移正相关(P<0.05),与性别、年龄、组织学分级无统计学相关(P>0.05)。HPA 与MMP-9 有较高的共同阳性表达率。HPA 和MMP-9 表达呈正相关(P<0.05),其共同表达率与肿瘤对周围脏器浸润和淋巴结转移有相关(P<0.05)。 多因素分析显示HPA 和MMP-9 均非影响预后的独立因素。结论:HPA 、MMP-9 在胰腺癌组织中的表达可能与胰腺癌浸润、转移相关,可作为新的胰腺癌标记物用于联合检测,具有重要的临床意义。且MMP-9 可能上调HPA 表达水平,促进HPA 介导的肿瘤浸润转移。

     

    Abstract: Objective:To investigate the expression of heparanase (HPSE) and matrix metalloproteinase-9 (MMP- 9) in pancreatic carcinoma, chronic pancreatitis, normal pancreatic tissue and the correlation between the two, and to analyze the relationship among the proteins, the infiltration, and metastasis of pancreatic carcinoma. Methods:Immunohistochemi -cal staining (SP method) was used to measure the HPSE and MMP- 9 expressions in 92cases with pancreatic carcinoma, 24with chronic pancreatitis (CP) and10with normal pancreatic tissue samples. The correlation between the expression of HPSE and MMP-9 and the clinico-pathologic index was analyzed and Pearson rank correlation analysis was set up for sta -tistical treatment. Results: The expression of HPSE was significantly higher in pancreatic carcinoma than in chronic pancre -atitis and normal pancreatic tissue ( P<0.05). The positive expression of HPSE protein had a positive correlation with the in -filtration of peripheral tissue and lymph node metastasis ( P<0.05), and had a negative correlation with the gender, age and histological grading (P>0.005 ). The expression of MMP-9 was significantly higher in the pancreatic carcinoma than in the chronic pancreatitis and normal pancreas (P<0.05). The positive expression of MMP- 9 protein positively correlated with the infiltration of peripheral tissue and the distant metastasis (P<0.05), and correlated negatively with the sex, age, and tumor differentiation of patients ( P>0.005 ). Both HPSE and MMP- 9 had a positive co-expression rate in pancreatic carcinoma. The expressions of HPSE correlated positively with that of MMP-9 in pancreatic carcinomas ( P<0.05). The co-expression rate related to the tumor infiltration of other peripheral organs and nodal metastases ( P<0.05). Multivariate analysis showed that neither HPSE nor MMP- 9 were independent prognostic factors. Conclusion:HPSE and MMP-9 expression in pancreat-ic carcinoma may be associated with the infiltration and metastasis of carcinoma. These should be regarded as the new markers of pancreatic carcinoma for combined detection, with important clinical significance. MMP-9 may also up-regulate the level of HPSE expression, and facilitate the HPSE-mediated tumor infiltration and metastasis.

     

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