Expression of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 in normal and malignant tissues of gastrointestinal tract.
Expression of serine protease SNC19/matriptase and its inhibitor hepatocyte growth factor activator inhibitor type 1 in normal and malignant tissues of gastrointestinal tract.
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DOI：
10.3748/wjg.v11.i39.6202
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发表时间：
2005-10
影响因子：
4.3
通讯作者：
Lei Zeng;Jiang Cao;Xing Zhang
中科院分区：
文献类型：
--
作者：
Lei Zeng;Jiang Cao;Xing Zhang
目的研究丝氨酸蛋白酶SNC 19/matriptase及其抑制剂hepatocyte growth factor activator inhibitor type 1（HAI-1）在胃肠道正常组织和恶性肿瘤组织中的表达，为进一步研究其与肿瘤进展和转移的关系奠定基础。方法从37例大肠癌组织、40例胃癌组织及癌旁正常组织中提取总RNA。以甘油醛-3-磷酸脱氢酶为内标物，采用实时荧光定量PCR检测SNC 19/matriptase和HAI-1的表达，并与临床病理参数进行相关性分析。结果HAI-1和SNC 19/matriptase在胃癌组织中的表达显著低于癌旁正常组织（Z =-3.280，P = 0.006; Z =-4.651，P = 0.000）。HAI-1：SNC 19/matriptase比值在正常组织和恶性组织中无显著性差异（P>0.05）。临床病理参数分析显示，与I/II期相比，III/IV期胃肿瘤的HAI-1表达和HAI-1：SNC 19/matriptase比率降低淋巴结阳性胃癌组织与淋巴结阴性胃癌组织比较（Z =-2.140，P = 0.031; Z =-2.155，P = 0.031），差异有统计学意义（Z =-2.081，P = 0.036; Z =-2.686，P = 0.006）。SNC 19/matriptase的表达与肿瘤分期、淋巴结转移无关（P>0.05）。HAI-1和HAI-1：SNC 19/matriptase比值在高分化胃癌组织中表达增高，但差异无统计学意义（P>0.05）。SNC 19/matriptase在不同分化程度胃癌组织中的表达差异无统计学意义（P>0.05）。大肠癌组织中HAI-1和SNC 19/matriptase的表达也显著低于癌旁正常组织（Z =-3.100，P = 0.002; Z =-2.731，P = 0.006），而HAI-1：SNC 19/matriptase的比值无差异。HAI-1表达降低与胃癌浸润深度和淋巴结转移有关，但无统计学意义（P>0.05）。SNC 19/matriptase的表达及HAI-1：SNC 19/matriptase的比值在不同分期、不同淋巴结转移情况下差异无统计学意义（P>0.05）。SNC 19/matriptase、HAI-1及HAI-1：SNC 19/martiptase比值在不同分化程度大肠癌组织中的表达差异无统计学意义（P>0.05）。结论SNC 19/matriptase及其抑制剂HAI-1在胃肠道肿瘤组织中的表达较正常胃肠道组织明显降低，HAI-1的表达降低可能与胃肠道肿瘤的浸润和淋巴结转移有关。可能涉及的机制需要进一步研究。
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.