Versican和TGF-β1在胃癌中的表达及临床意义
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摘要
目的:研究胃癌组织中Versican和TGF-β1的表达及其与胃癌细胞增殖的关系。方法:用免疫组织化学方法检测80例胃癌组织和30例癌旁正常组织中Versican、TGF-β1和Ki-67的表达。结果:Versican在胃癌中的阳性率显著高于正常胃黏膜(P=0.001)。主要表达于胃癌间质纤维母细胞的胞浆,且与胃癌的分化程度、临床分期及淋巴结转移显著相关(P<0.05);胃癌中TGF-β1的阳性率和Ki-67表达均显著高于正常胃黏膜(P<0.001),且均与浸润深度、临床分期和淋巴结转移相关(P<0.05);在胃癌组织中Versican与TGF-β1的表达呈正相关(r=0.256,P=0.022)。结论:胃癌组织中Versican和TGF-β1的表达异常增高,二者均可促进胃癌细胞的生长,并且与胃癌的临床病理特征有关,为胃癌的治疗提供了潜在的靶点。
Objective:To study the expression of Versican and TGF-β1 in gastric cancer and their relationship with cancer cells proliferation.Methods:We detected the expression of Versican,TGF-β1 and Ki-67 in 80 cases of gastric cancer and 30 cases of normal gastric tissue by immunohistochemistry.Results:The expression of Versican was significantly higher in gastric cancer than that in normal gastric tissue(P=0.001).The expression of Versican was mainly in tumor associated fibroblasts,and was related to differentiation degree,clinical stage,and lymph node metastasis(P<0.05).There were statistically significant differences in expression of TGF-β1 and Ki-67 between gastric cancer and normal gastric tissue(P<0.001 respectively).Both the expression of TGF-β1 and Ki-67 in gastric cancer were associated with depth of tumor invasion,clinical stage and lymph node metastasis(P<0.05).Positive correlation of Versican and TGF-β1 protein expression was found in gastric cancer(r=0.256,P<0.01).Conclusion:The expression of Versican and TGF-β1 in gastric cancer was increased abnormally.Both of them could promote the growth of gastric cancer cells and be related to the clinicopathological characteristics of gastric cancer,which provided a potential target for the treatment of gastric cancer.
Objective:To study the expression of Versican and TGF-β1 in gastric cancer and their relationship with cancer cells proliferation.Methods:We detected the expression of Versican,TGF-β1 and Ki-67 in 80 cases of gastric cancer and 30 cases of normal gastric tissue by immunohistochemistry.Results:The expression of Versican was significantly higher in gastric cancer than that in normal gastric tissue(P=0.001).The expression of Versican was mainly in tumor associated fibroblasts,and was related to differentiation degree,clinical stage,and lymph node metastasis(P<0.05).There were statistically significant differences in expression of TGF-β1 and Ki-67 between gastric cancer and normal gastric tissue(P<0.001 respectively).Both the expression of TGF-β1 and Ki-67 in gastric cancer were associated with depth of tumor invasion,clinical stage and lymph node metastasis(P<0.05).Positive correlation of Versican and TGF-β1 protein expression was found in gastric cancer(r=0.256,P<0.01).Conclusion:The expression of Versican and TGF-β1 in gastric cancer was increased abnormally.Both of them could promote the growth of gastric cancer cells and be related to the clinicopathological characteristics of gastric cancer,which provided a potential target for the treatment of gastric cancer.
引文
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[16] Li Zhen,Miao Zhifeng,Sun Gongping et al.TGF-β1 induces SGC-7901 adhesion,proliferation and migration[J].Chin J Cancer Prev Treat,2012,19(15):1121-1123.[李震,苗志峰,孙公平,等.TGF-β1对胃癌细胞SGC- 7901转移潜能影响的研究[J].中华肿瘤防治杂志,2012,19(15):1121-1123.]
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[18] Van Bockstal M,Lambein K.Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion[J].Oncoscience,2014,10:634-648.
[19] Tsz-Lun Yeung,Cecilia S Leung,Kwong-Kwok Wong,et al.TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment[J].Cancer Res,2013,3(16):5016-5028.
[2] Gore J,Imasuen-Williams IE,Conteh AM,et al.Combined targeting of TGF-β,EGFR and HER2 suppresses lymphangiogenesis and metastasis in a pancreatic cancer model[J].Cancer Lett,2016,379:143-153.
[3] Yang YC,Tang XP,Yu L,et al.Correlation between gene polymorphisms of transforming growth factor β1 and malignant tumor of digestive tract[J].Medical Recapitulate,2015,21(18):3310-3312.[杨颖丞,唐小平,喻林,等.转化生长因子β1基因多态性与消化道恶性肿瘤的相关性[J].医学综述,2015,21(18):3310-3312.]
[4] Evanko SP,Chan CK,Johnson PY,et al.The biochemistry and immunohistochemistry of versican[J].Methods Cell Biol,2018,14(3):261-279.
[5] Andersson-Sjoland A,Hallgren O,Rolandsson S,et al.Versican in inflammation and tissue remodeling:The impact on lung disorders[J].Glycobiology,2015.25,243-251.
[6] Gupta N.Versican and its associated molecules:Potential diagnostic markers for multiple myeloma[J].Clinica Chimica Acta,2015,442:119-124.
[7] Wight TN.Provisional matrix:A role for versican and hyaluronan[J].Matrix Biology,2017,60:38-56.
[8] Keire PA,Bressler SL,Lemire JM,A role for versican in the development of leiomyosarcoma[J].J Biol Chem,2014,289(49):34089-34103.
[9] Rangel MP,De Sá VK,Prieto T,et al.Biomolecular analysis of matrix proteoglycans as biomarkers in non small cell lung cancer[J].Glycoconj J,2018,35(2):233-242.
[10] Asano K,Nelson CM,Nandadasa S,et al.Stromal versican regulates tumor growth by promoting angiogenesis[J].Sci Rep,2017,7(1):17225.
[11] Yang ML,Wang LF,Yang JH,et al.Expression of Versican and its clinical significance in gastric carcinoma[J].Chinese Journal of Pathplogy,2014,43(7):473-477.[杨迷玲,王立峰,杨金花,等.Versican在胃癌中的表达及其临床意义[J].中华病理学杂志,2014,43(7):473-477.]
[12] Shun Chida,Hirokazu Okayama,Masaru Noda,et al.Stromal VCAN expression as a potential prognostic biomarker for disease recurrence in stage Ⅱ-Ⅲ colon cancer[J].Carcinogenesis,2016,9:878-887.
[13] Yozo M,Hiroaki S,Taku K,et al.Versican promotes tumor progression,metastasis and predicts poor prognosis in renal carcinoma[J].Mol Cancer Res,2017,15(7):884-895.
[14] Wu YC,Tang SJ,Sun GH,et al.CXCR7 mediates TGFbeta1-promoted EMT and tumor-initiating features in lung cancer[J].Oncogene,2016,35:2123-2132.
[15] Ameet K Mishra,Christopher R Parish,Ma Liwong,et al.Leptin signals via TGF-β1 to promote metastatic potential and stemness in breast cancer[J].PLoS One,2017,12(5):e0178454.
[16] Li Zhen,Miao Zhifeng,Sun Gongping et al.TGF-β1 induces SGC-7901 adhesion,proliferation and migration[J].Chin J Cancer Prev Treat,2012,19(15):1121-1123.[李震,苗志峰,孙公平,等.TGF-β1对胃癌细胞SGC- 7901转移潜能影响的研究[J].中华肿瘤防治杂志,2012,19(15):1121-1123.]
[17] Edwards IJ.Proteoglycans in prostate cancer[J].Nat Rev Urol,2012,9:196-206.
[18] Van Bockstal M,Lambein K.Differential regulation of extracellular matrix protein expression in carcinoma-associated fibroblasts by TGF-β1 regulates cancer cell spreading but not adhesion[J].Oncoscience,2014,10:634-648.
[19] Tsz-Lun Yeung,Cecilia S Leung,Kwong-Kwok Wong,et al.TGF-β modulates ovarian cancer invasion by upregulating CAF-derived versican in the tumor microenvironment[J].Cancer Res,2013,3(16):5016-5028.
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