Wnt5a、MMP2和MMP14在胃癌中的表達及其對臨床病理特征的影響_《中國普外基礎與臨床雜志》

作者：

江州華 ¹ , 吳生華 ¹ , 李小強 ² , 俞繼衛 ¹ , 姜波健 ¹

1.上海交通大學醫學院附屬第三人民醫院普外科(上海 201900);;
2.上海交通大學醫學院附屬第三人民醫院病理科(上海 201900);

關鍵詞：

胃癌侵襲轉移上皮間質轉型 Wnt5a 基質金屬蛋白酶2 基質金屬蛋白酶14/MT1-MMP

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目的　研究Wnt5a、MMP2及MMP14在胃癌原發灶中的表達，探討三者之間的相關性及其與臨床病理特征的關系。
方法　免疫組化染色法檢測106例胃癌手術標本及其中的39例正常胃組織中Wnt5a、MMP2和MMP14的表達，χ2檢驗和非參數檢驗分析三者間的關系及其與臨床病理參數的關系。
結果　Wnt5a、MMP2及MMP14在胃癌原發灶中廣泛表達,均明顯高于正常胃組織中的表達（P lt;0.05）。Wnt5a陽性表達者的腫瘤直徑更大、浸潤深度更深、區域淋巴結轉移程度更高、TNM分期更晚、淋巴結轉移率更高、存在淋巴管和血管浸潤　（P lt;0.05）。
MMP2和MMP14陽性表達者的浸潤深度更深、區域淋巴結轉移程度更高、TNM分期更晚及淋巴結轉移率更高（P lt;0.05），且均存在淋巴管浸潤（P lt;0.05）,但均與血管浸潤與否無關。此外，MMP2陽性表達者的腫瘤直徑更大（P lt;0.05）。Spearman秩相關分析顯示，Wnt5a和MMP2（rs=0.240，P=0.014）、Wnt5a和MMP14　（rs=0.251，P=0.010）、MMP2和MMP14（rs=0.444，P=0.000）兩兩之間表達均存在正相關性。
結論　Wnt5a、MMP2及MMP14的表達或能促進胃癌侵襲和轉移，且三者之間的表達呈正相關。

引用本文： 江州華 ,吳生華,李小強,俞繼衛,姜波健. Wnt5a、MMP2和MMP14在胃癌中的表達及其對臨床病理特征的影響. 中國普外基礎與臨床雜志, 2010, 17(10): 1077-1082. doi: 復制

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14.	Fernandez-Cobo M, Zammarchi F, Mandeli J, et al. Expression of Wnt5A and Wnt10B in non-immortalized breast cancer cells [J]. Oncol Rep, 2007; 17(4): 903-907.
15.	Kurayoshi M, Oue N, Yamamoto H, et al. Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion [J]. Cancer Res, 2006; 66(21): 10439-10448.
16.	江州華, 俞繼衛, 姜波健. 基質金屬蛋白酶對胃癌微環境調控作用的研究進展 [J]. 中國普外基礎與臨床雜志, 2009; 16(9): 768-772.
17.	王鵬, 郭琳, 王強. PTEN、Fas/FasL和MMP-2在胃癌組織的表達及其臨床意義 [J]. 中國普外基礎與臨床雜志, 2009; 12(16): 991-995.
18.	Koyama S. Enhanced Cell surface expression of matrix metalloproteinases and their inhibitors and tumor-induced host response in progression of human gastric cancer [J]. Dig Dis Sci, 2004; 49(10): 1621-1630.
19.	Zheng H, Takahashi H, Murai Y, et al. Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma [J]. Anticancer Res, 2006; 26(5A): 3579-3583.
20.	Shim KN, Jung SA, Joo YH, et al. Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer [J]. J Gastroenterol, 2007; 42(2): 120-128.
21.	Orlichenko LS, Radisky DC. Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development [J]. Clin Exp Metastasis, 2008; 25(6): 593-600.
22.	Coyle RC, Latimer A, Jessen JR. Membrane-type 1 matrix metalloproteinase regulates cell migration during zebrafish gastrulation: evidence for an interaction with non-canonical Wnt signaling [J]. Exp Cell Res, 2008; 314(10): 2150-2162.
23.	Cao J, Chiarelli C, Richman O, et al. Membrane type 1 matrix metalloproteinase induces epithelial-to-mesenchymal transition in prostate cancer [J]. J Biol Chem, 2008; 283(10): 6232-6240.

1. 　吳春曉，鄭瑩，鮑萍萍, 等. 上海市胃癌發病流行現況與時間趨勢分析 [J]. 外科理論與實踐, 2008; 13(1): 24-29.
2. 　Wu Y, Zhou BP. New insights of epithelial-mesenchymal transition in cancer metastasis [J]. Acta Biochim Biophys Sin (Shanghai), 2008; 40(7): 643-650.
3. 　Yu JW, Wu JG, Zheng LH, et al. Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma [J]. J Exp Clin Cancer Res, 2009; 28: 55.
4. 　Yu JW, Wu JG, Jiang BJ, et al. Study on lymph node metastasis correlated to lymphangiogenesis, lymphatic vessel invasion and lymph node micrometastasis in gastric cancer [J]. J Surg Res, 2009; 11.doi:10.1016/j.jss.2009.10.030.
5. 　Wodarz A, Nusse R. Mechanisms of Wnt signaling in development [J]. Annu Rev Cell Dev Biol, 1998; 14: 59-88.
6. 　Lustig B, Behrens J. The Wnt signaling pathway and its role in tumor development [J]. Cancer Res Clin Oncol, 2003; 129(4): 199-221.
7. 　劉臻, 崔東旭, 劉寶林, 等. β-連環素基因在乳腺增生及癌組織中表達和突變的研究 [J]. 中國普外基礎與臨床雜志, 2007; 11(14): 685-688.
8. 　Topol L, Jiang X, Choi H, et al. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent β-catenin degradation [J]. J Cell Biol, 2003; 162(5): 899-908.
9. 　Mikels AJ, Nusse R. Purified Wnt5a protein activatesor inhibits β-catenin-TCF signaling depending on receptor context [J]. PLoS Biol, 2006; 4(4): 570-582.
10. 　Kremenevskaja N, von Wasielewski R, Rao AS, et al. Wnt-5a has tumor suppressor activity in thyroid carcinoma [J]. Oncogene, 2005; 24(13): 2144-2154.
11. 　Liu XH, Pan MH, Lu ZF, et al. Expression of Wnt-5a and its clinicopathological significance in hepatocellular carcinoma [J]. Dig Liver Dis, 2008; 40(7): 560-567.
12. 　Da Forno PD, Pringle JH, Hutchinson P, et al. WNT5A expression increases during melanoma progression and correlates with outcome [J]. Clin Cancer Res, 2008; 14(18): 5825-5832.
13. 　Wang Q, Williamson M, Bott S, et al. Hypomethylation of WNT5A, CRIP1 and S100P in prostate cancer [J]. Oncogene, 2007; 26(45): 6560-6565.
14. 　Fernandez-Cobo M, Zammarchi F, Mandeli J, et al. Expression of Wnt5A and Wnt10B in non-immortalized breast cancer cells [J]. Oncol Rep, 2007; 17(4): 903-907.
15. 　Kurayoshi M, Oue N, Yamamoto H, et al. Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion [J]. Cancer Res, 2006; 66(21): 10439-10448.
16. 　江州華, 俞繼衛, 姜波健. 基質金屬蛋白酶對胃癌微環境調控作用的研究進展 [J]. 中國普外基礎與臨床雜志, 2009; 16(9): 768-772.
17. 　王鵬, 郭琳, 王強. PTEN、Fas/FasL和MMP-2在胃癌組織的表達及其臨床意義 [J]. 中國普外基礎與臨床雜志, 2009; 12(16): 991-995.
18. 　Koyama S. Enhanced Cell surface expression of matrix metalloproteinases and their inhibitors and tumor-induced host response in progression of human gastric cancer [J]. Dig Dis Sci, 2004; 49(10): 1621-1630.
19. 　Zheng H, Takahashi H, Murai Y, et al. Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma [J]. Anticancer Res, 2006; 26(5A): 3579-3583.
20. 　Shim KN, Jung SA, Joo YH, et al. Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer [J]. J Gastroenterol, 2007; 42(2): 120-128.
21. 　Orlichenko LS, Radisky DC. Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development [J]. Clin Exp Metastasis, 2008; 25(6): 593-600.
22. 　Coyle RC, Latimer A, Jessen JR. Membrane-type 1 matrix metalloproteinase regulates cell migration during zebrafish gastrulation: evidence for an interaction with non-canonical Wnt signaling [J]. Exp Cell Res, 2008; 314(10): 2150-2162.
23. 　Cao J, Chiarelli C, Richman O, et al. Membrane type 1 matrix metalloproteinase induces epithelial-to-mesenchymal transition in prostate cancer [J]. J Biol Chem, 2008; 283(10): 6232-6240.

《中國普外基礎與臨床雜志》

Wnt5a、MMP2和MMP14在胃癌中的表達及其對臨床病理特征的影響

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《中國普外基礎與臨床雜志》

Wnt5a、MMP2和MMP14在胃癌中的表達及其對臨床病理特征的影響

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

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