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丝氨酸蛋白酶SNC19/胃蛋白酶及1型肝细胞生长因子激活剂抑制剂在胃肠道正常组织和恶性组织中的表达

Expression of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 in normal and malignant tissues of gastrointestinal tract.

作者信息

Zeng Lei, Cao Jiang, Zhang Xing

机构信息

Clinical Research Institute, Sir Run Run Shaw Hospital, Zhejiang University, 3 East Qingchun Road, Hangzhou 310016, Zhejiang Province, China.

出版信息

World J Gastroenterol. 2005 Oct 21;11(39):6202-7. doi: 10.3748/wjg.v11.i39.6202.

Abstract

AIM

To provide the expression profile of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 (HAI-1) in normal and malignant tissues of gastrointestinal tract at mRNA level for further study on their correlations with tumor progression and metastasis.

METHODS

Total RNAs were prepared from 37 samples of colorectal cancer tissues, 40 samples of gastric cancer tissues, and their adjacent normal tissues. The expression of SNC19/matriptase and HAI-1 in these samples was detected by real-time fluorescent quantitative PCR using glyceraldehyde-3-phosphate dehydrogenase as internal standard, and the clinical significance for the correlation with clinicopathological parameters was evaluated.

RESULTS

In gastric cancer tissues the expression of HAI-1 and SNC19/matriptase was significantly lower than that in the corresponding adjacent normal tissues (Z = -3.280, P = 0.006; Z = -4.651, P = 0.000). HAI-1:SNC19/matriptase ratio showed no difference between normal and malignant tissues (P>0.05). Analysis of clinicopathological parameters showed decreased expression of HAI-1 and HAI-1:SNC19/matriptase ratio associated with stage III/IV gastric tumors as compared to stage I/II ones (Z = -2.140, P = 0.031; Z = -2.155, P = 0.031), and with lymph node-positive gastric cancer tissues as compared to lymph node-negative ones (Z = -2.081, P = 0.036; Z = -2.686, P = 0.006). The expression of SNC19/matriptase had no relationship with stages and lymph node metastasis (P>0.05). The expression of HAI-1 and HAI-1:SNC19/matriptase ratio increased in well-differentiated gastric cancer tissues, but there was no statistical significance (P>0.05). The difference of SNC19/matriptase expression was not significant in gastric cancer tissues of different histological differentiation status (P>0.05). In colorectal cancer tissues, the expression of HAI-1 and SNC19/matriptase was also markedly lower than that in their adjacent normal tissues (Z = -3.100, P = 0.002; Z = -2.731, P = 0.006), whereas HAI-1:SNC19/matriptase ratio showed no difference. Decreased expression of HAI-1 was associated with increased invasive depth and lymph node metastasis, but there was no statistical significance (P>0.05). The difference of SNC19/matriptase expression and HAI-1:SNC19/matriptase ratio was not significant in different stages and different lymph node metastasis status (P>0.05). The expression of SNC19/matriptase, HAI-1 or HAI-1:SNC19/martiptase ratio showed no difference in colorectal cancer tissues of different histological differentiation status (P>0.05).

CONCLUSION

The expressions of SNC19/matriptase and its inhibitor HAI-1 are decreased in gastrointestinal cancer tissues compared to their normal counterparts, and the decreased expression of HAI-1 may correlate with invasion and lymph node metastasis. The possible mechanisms involved need to be further investigated.

摘要

目的

在mRNA水平上提供丝氨酸蛋白酶SNC19/胃蛋白酶及1型肝细胞生长因子激活剂抑制剂(HAI-1)在胃肠道正常组织和恶性组织中的表达谱,以进一步研究它们与肿瘤进展和转移的相关性。

方法

从37例结直肠癌组织、40例胃癌组织及其癌旁正常组织中提取总RNA。以甘油醛-3-磷酸脱氢酶为内参,采用实时荧光定量PCR检测这些样本中SNC19/胃蛋白酶和HAI-1的表达,并评估其与临床病理参数相关性的临床意义。

结果

胃癌组织中HAI-1和SNC19/胃蛋白酶的表达显著低于相应的癌旁正常组织(Z = -3.280,P = 0.006;Z = -4.651,P = 0.000)。HAI-1:SNC19/胃蛋白酶比值在正常组织和恶性组织之间无差异(P>0.05)。临床病理参数分析显示,与Ⅰ/Ⅱ期胃癌相比,Ⅲ/Ⅳ期胃癌组织中HAI-1表达及HAI-1:SNC19/胃蛋白酶比值降低(Z = -2.140,P = 0.031;Z = -2.155,P = 0.031),与淋巴结阳性胃癌组织相比,淋巴结阴性胃癌组织中HAI-1表达及HAI-1:SNC19/胃蛋白酶比值降低(Z = -2.081,P = 0.036;Z = -2.686,P = 0.006)。SNC19/胃蛋白酶的表达与分期及淋巴结转移无关(P>0.05)。高分化胃癌组织中HAI-1表达及HAI-1:SNC19/胃蛋白酶比值升高,但无统计学意义(P>0.05)。不同组织学分化状态的胃癌组织中SNC19/胃蛋白酶表达差异无统计学意义(P>0.05)。在结直肠癌组织中,HAI-1和SNC19/胃蛋白酶的表达也明显低于其癌旁正常组织(Z = -3.100,P = 0.002;Z = -2.731,P = 0.006),而HAI-1:SNC19/胃蛋白酶比值无差异。HAI-1表达降低与浸润深度增加和淋巴结转移有关,但无统计学意义(P>0.05)。不同分期和不同淋巴结转移状态的结直肠癌组织中SNC19/胃蛋白酶表达及HAI-1:SNC19/胃蛋白酶比值差异无统计学意义(P>0.05)。不同组织学分化状态的结直肠癌组织中SNC19/胃蛋白酶、HAI-1表达及HAI-1:SNC19/胃蛋白酶比值差异无统计学意义(P>0.05)。

结论

与正常组织相比,胃肠道癌组织中SNC19/胃蛋白酶及其抑制剂HAI-1的表达降低,HAI-1表达降低可能与侵袭和淋巴结转移相关。其中涉及的可能机制有待进一步研究。

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