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基质金属蛋白酶-9、E-钙黏蛋白和血管内皮生长因子的表达与胃癌临床病理特征及化疗敏感性反应的关系

Relationships of MMP-9, E-cadherin, and VEGF expression with clinicopathological features and response to chemosensitivity in gastric cancer.

作者信息

Gao Hongyu, Lan Xiuwen, Li Sen, Xue Yingwei

机构信息

Department of Gastroenterology Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.

出版信息

Tumour Biol. 2017 May;39(5):1010428317698368. doi: 10.1177/1010428317698368.

Abstract

The matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor play an important role in behavior of tumor cell growth, invasion, and metastasis. In this study, we investigated the relationships of matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor expression with clinicopathological features and results of chemosensitivity tested by collagen gel droplet-embedded culture-drug sensitivity test in gastric cancer. Fresh specimens were used for collagen gel droplet-embedded culture-drug sensitivity test and paired fixed specimens were used for immunohistochemistry. Positive expression of matrix metalloproteinase-9 was associated with poorly differentiated carcinoma (p = 0.032), lymph node metastasis (p = 0.022), and tumor stage (p = 0.023). Negative expression of E-cadherin was associated with poorly differentiated carcinoma (p = 0.007), lymph node metastasis (p = 0.012), and tumor stage (p = 0.007). Positive expression of vascular endothelial growth factor was associated with tumor size (p = 0.040) and stage (p = 0.007). Collagen gel droplet-embedded culture-drug sensitivity test was successfully evaluated in 56 patients. Among them, 29 (51.7%) patients were resistant to TS-1 and 31 (55.3%) patients were resistant to L-OHP. The L-OHP resistance rate in vascular endothelial growth factor positive patients was significantly higher than that in negative patients (p = 0.031). The L-OHP resistance rate in E-cadherin negative patients was significantly higher than that in positive patients (p = 0.014). In conclusion, matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor were involved in tumor invasion and metastasis. Positive expression of matrix metalloproteinase-9 and vascular endothelial growth factor and negative expression of E-cadherin were malignant markers for gastric cancer. Positive expression of vascular endothelial growth factor and negative expression of E-cadherin were associated with L-OHP resistance.

摘要

基质金属蛋白酶-9、E-钙黏蛋白和血管内皮生长因子在肿瘤细胞生长、侵袭及转移行为中发挥重要作用。在本研究中,我们通过胶原凝胶滴包埋培养-药物敏感性试验,研究了基质金属蛋白酶-9、E-钙黏蛋白和血管内皮生长因子表达与胃癌临床病理特征及化疗敏感性结果之间的关系。新鲜标本用于胶原凝胶滴包埋培养-药物敏感性试验,配对的固定标本用于免疫组织化学检测。基质金属蛋白酶-9阳性表达与低分化癌(p = 0.032)、淋巴结转移(p = 0.022)及肿瘤分期(p = 0.023)相关。E-钙黏蛋白阴性表达与低分化癌(p = 0.007)、淋巴结转移(p = 0.012)及肿瘤分期(p = 0.007)相关。血管内皮生长因子阳性表达与肿瘤大小(p = 0.040)及分期(p = 0.007)相关。56例患者成功完成胶原凝胶滴包埋培养-药物敏感性试验。其中,29例(51.7%)患者对替吉奥耐药,31例(55.3%)患者对奥沙利铂耐药。血管内皮生长因子阳性患者的奥沙利铂耐药率显著高于阴性患者(p = 0.031)。E-钙黏蛋白阴性患者的奥沙利铂耐药率显著高于阳性患者(p = 0.014)。总之,基质金属蛋白酶-9、E-钙黏蛋白和血管内皮生长因子参与肿瘤侵袭和转移。基质金属蛋白酶-9和血管内皮生长因子的阳性表达以及E-钙黏蛋白的阴性表达是胃癌的恶性标志物。血管内皮生长因子的阳性表达和E-钙黏蛋白的阴性表达与奥沙利铂耐药相关。

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