乙酰肝素酶基因、CD44v6、基质金属蛋白酶-7及nm23蛋白的表达及其与胃癌侵袭和转移的关系。
Expression of heparanase gene, CD44v6, MMP-7 and nm23 protein and their relationship with the invasion and metastasis of gastric carcinomas.
作者信息
Chen Jun-Qiang, Zhan Wen-Hua, He Yu-Long, Peng Jun-Sheng, Wang Jian-Ping, Cai Shi-Rong, Ma Jin-Ping
机构信息
Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
出版信息
World J Gastroenterol. 2004 Mar 15;10(6):776-82. doi: 10.3748/wjg.v10.i6.776.
AIM
To explore the expression of heparanase gene, CD44v6, MMP-7 and nm23 proteins in human gastric carcinoma as well as their relationship with the clinicopathological factors.
METHODS
Reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expressions of heparanase mRNA in 43 human gastric carcinomas and 10 adjacent normal gastric tissues. Streptavidin-peroxidase (S-P) two step method was used to measure the immunohistochemical expression of CD44v6, MMP-7 and nm23 protein in 43 human gastric carcinomas.
RESULTS
The expression of heparanase gene was positive in 29 cases of gastric cancer with a positive rate of 67.4%, which was significantly higher than those in adjacent normal gastric tissues (P<0.05). The heparanase mRNA expression was significantly related to advanced stage of disease, serosal infiltration, lymph node metastasis and size of tumors (P<0.05), but not related to tumor location, gross and histological types of the cancer, peritoneal dissemination and liver metastasis (P>0.05). The positive rate of CD44v6, nm23 and MMP-7 proteins was 76.7%, 37.2% and 60.5%, respectively. The CD44v6 protein expression was significantly related to serosal infiltration, lymph node metastasis and TNM stage of disease (P<0.05). The nm23 protein expression was significantly related to the tumor gross appearance, lymph node and peritoneal metastasis (P<0.05). The MMP-7 protein expression was significantly related to serosal infiltration and TNM stage of disease (P<0.05). In an attempt to measure the association between these agents, we found that the expression of heparanase mRNA had significantly negative correlation with the expression of CD44v6 and MMP-7 protein (P<0.05), the expression of MMP-7 protein had significantly positive correlation with the expression of CD44v6 protein (r=0.568, P<0.05), the expression of MMP-7 protein had no correlation with the expression of nm23 protein (P>0.05), and the expression of nm23 protein had no correlation with the expression of CD44v6 protein (P>0.05).
CONCLUSION
Despite their different mechanisms of action, heparanase, CD44v6 and nm23 may play important roles in the invasive infiltration and lymph node metastasis in gastric carcinomas. Instead of metastatic spreading, MMP-7 may be just related to the invasion of gastric carcinomas. However, co-detection of these factors may be important to predict metastatic spreading in such patients.
目的
探讨乙酰肝素酶基因、CD44v6、基质金属蛋白酶-7（MMP-7）及nm23蛋白在人胃癌中的表达及其与临床病理因素的关系。
方法
采用逆转录聚合酶链反应（RT-PCR）检测43例人胃癌组织及10例癌旁正常胃组织中乙酰肝素酶mRNA的表达。采用链霉亲和素-过氧化物酶（S-P）两步法检测43例人胃癌组织中CD44v6、MMP-7及nm23蛋白的免疫组化表达。
结果
29例胃癌组织中乙酰肝素酶基因表达阳性，阳性率为67.4%，显著高于癌旁正常胃组织（P<0.05）。乙酰肝素酶mRNA表达与疾病晚期、浆膜浸润、淋巴结转移及肿瘤大小显著相关（P<0.05），但与肿瘤部位、大体类型、组织学类型、腹膜播散及肝转移无关（P>0.05）。CD44v6、nm23及MMP-7蛋白的阳性率分别为76.7%、37.2%及60.5%。CD44v6蛋白表达与浆膜浸润、淋巴结转移及疾病TNM分期显著相关（P<0.05）。nm23蛋白表达与肿瘤大体形态、淋巴结及腹膜转移显著相关（P<0.05）。MMP-7蛋白表达与浆膜浸润及疾病TNM分期显著相关（P<0.05）。为了检测这些因子之间的关联，我们发现乙酰肝素酶mRNA表达与CD44v6及MMP-7蛋白表达呈显著负相关（P<0.05），MMP-7蛋白表达与CD44v6蛋白表达呈显著正相关（r=0.568，P<0.05），MMP-7蛋白表达与nm23蛋白表达无相关性（P>0.05），nm23蛋白表达与CD44v6蛋白表达无相关性（P>0.05）。
结论
尽管乙酰肝素酶、CD44v6及nm23作用机制不同，但它们可能在胃癌的侵袭浸润及淋巴结转移中发挥重要作用。MMP-7可能仅与胃癌的侵袭有关，而非转移扩散。然而，联合检测这些因子对预测此类患者的转移扩散可能具有重要意义。
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