肝素酶和趋化因子受体7表达对胃癌侵袭及预后的影响

Significance of Heparanase and Chemokines Receptors 7 in Invasion and Prognosis of Gastric Carcinoma

【目的】观察肝素酶、趋化因子受体7（CCR7）的表达对胃癌侵袭和淋巴结转移潜能的影响以及两者的相关性。【方法】临床收集行胃癌根治性切除（淋巴结清扫）的56例胃癌患者的原发癌组织、癌旁组织、淋巴结组织,另选30例正常胃黏膜组织石蜡标本作为正常对照组。采用免疫组化S-P法及RT-PCR法检测上述组织中肝素酶、趋化因子受体7蛋白和m RNA的表达,应用χ~2检验比较肝素酶、CCR7表达差异,Logistic多因素回归分析判定胃癌淋巴结转移的独立相关因素,生存率比较应用Log-rank检验,相关性用Spearman等级相关分析。【结果】胃癌组织肝素酶、CCR7蛋白表达阳性率分别为48.2%和41.1%,显著高于癌旁组织8.9%和7.1%,正常胃组织3.6%和1.8%（P=0.008）;胃癌组织中乙酰肝素酶、CCR7m RNA的表达亦高于癌旁和正常组织,差异有统计学意义（P=0.009和P=0.000）,癌旁和正常组织的表达相近（P=0.316）。肝素酶表达与肿瘤分化程度无关,但与肿瘤直径、脉管侵犯、淋巴结转移、远处转移、浆膜受累和TNM分期等密切相关;CCR7表达与肿瘤的侵袭深度无关,但与淋巴结转移和N分期等有关;胃癌组织中CCR7（OR=10.365,P=0.000）及肝素酶的阳性表达（OR=5.604,P=0.016）是胃癌患者淋巴结转移的独立危险因素,而性别、年龄、肿瘤分化程度以及T分期都与胃癌淋巴结转移无明显相关（P=0.319）。肝素酶、CCR7阳性共表达组术后生存率明显低于阴性组（65.23%vs 21.53%,P=0.016）。胃癌组织中两者之间存在相关性（rs=0.341,P=0.026）。【结论】肝素酶参与胃癌的直接侵袭过程,CCR7与淋巴结转移关系密切,两者阳性共表达可成为判定胃癌预后较差的有用指标。

【Objective】 To investigate the potential affect and correlation of heparanase and chemokines receptors 7 to invasion and lymph node metastasis of human gastric carcinoma. 【Methods】 The expression of heparanase and chemokines receptors 7 in 56 cases of gastric cancer, adjacent tissues, lymph node tissue were studied by immunohistochemistry and RT-PCR. Another 30 cases of normal gastric mucosa as normal control group. χ2test was used to compare heparanase, CCR7 expression differences, Logistic regression analysis independent factors determine lymph node metastasis, Log-rank test to compare survival rate, Spearman rank correlation analysis determine correlation. 【Results】 The rate of heparanase and chemokines receptors 7 and their m RNA in tumor tissues（48.2% and 41.1%） were significantly higher than those in adjacent tissues of cancer（8.9% and 7.1%） and normal tissues（3.6% and 1.8%）（P = 0.008）. The m RNA of adjacent tissues of cancer and normal tissues） showed no significant difference（P =0.316）. Analysis of the clinicopathologic features showed stronger heparanase expression in the cases of huge growing tumors, venous invasion and regional lymph node metastasis, distant metastases, serosal infiltration, and TNM stage III-IV, but the expression of heparanase protein was not related with the histological grade of the tumor. The positive expression of CCR7 in the tumor tissues was significantly related with lymph node metastasis and N stage. The positive expression of CCR7（OR =10.365, P = 0.000） and heparanase（OR = 5.604, P = 0.016） in gastric carcinoma were independent risk factors in patients with lymph node metastasis, but the sex, age, tumor differentiation and T stage had no significant positive correlation with the lymph node metastasis（P = 0.319）. The survival rate of heparanase and CCR7 positive co-expression group was significantly lower than negative group（65.23% vs 21.53%,P？ 0.016）. There was a significant correlation between expression of heparanase and CCR7（rs= 0.341, P = 0.026）. 【Conclusion】The heparanase involve in the direct invasion of gastric cancer, CCR7 and lymph node metastasis are closely related, both positive co-expression can be determined to be useful indicators of poor prognosis of gastric cancer.