DAB2IP和β-catenin在胃癌组织中的表达及临床意义
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摘要
目的探讨DAB2相互作用蛋白(DAB2IP)和β-连环蛋白(β-catenin)在胃癌组织中的表达及其临床意义。方法选取95例行胃癌根治术患者的胃癌组织(n=95)及其癌旁正常黏膜组织(n=30)标本,采用免疫组织化学染色法检测两种组织中DAB2IP和β-catenin的表达情况,并分析其阳性表达与患者临床特征和生存时间的关系,采用Cox比例风险回归模型分析胃癌患者预后的影响因素。结果胃癌组织中β-catenin的阳性表达率明显高于癌旁正常黏膜组织,DAB2IP的阳性表达率明显低于癌旁正常黏膜组织(P<0.01)。DAB2IP阴性组中β-catenin的阳性表达率明显高于DAB2IP阳性组(P<0.01)。Spearman相关性分析结果显示,DAB2IP和β-catenin在胃癌组织中的表达呈明显负相关(r=-0.535,P<0.01)。不同TNM分期、浸润深度、远处转移情况和淋巴结转移情况胃癌患者胃癌组织中DAB2IP的阳性表达情况比较,差异均有统计学意义(P<0.05)。不同TNM分期、淋巴结转移情况、分化程度和浸润深度胃癌患者胃癌组织中β-catenin的阳性表达情况比较,差异均有统计学意义(P<0.05)。DAB2IP阳性表达组患者的生存时间长于DAB2IP阴性表达组(P<0.05)。β-catenin阴性表达组患者的生存时间长于阳性表达组患者(P<0.05)。有远处转移和DAB2IP阴性表达是影响胃癌患者预后的独立危险因素(P<0.01)。结论 DAB2IP在胃癌组织中的表达下调,β-catenin在的在胃癌组织中的表达上调,二者可作为胃癌诊断和预后评估的有效指标,但β-catenin不能作为提示胃癌预后的独立指标。
Objective To investigate the expression of disabled homolog 2-interacting protein(DAB2IP) and β-catenin in gastric cancer tissues and its clinical significance. Method Specimens of gastric cancer tissues(n=95) and normal mucosa tissue adjacent to the cancer(n=30) of 95 patients who had undergone radical surgery for gastric cancer were obtained. The expression of DAB2IP and β-catenin was detected by immunohistochemical staining methods between two types of tissue, to analyze the relationship between the positive expression of the above measurements and the clinical features and survival time of the patients. Cox regression model was used to analyze the prognostic factors in patients with gastric cancer. Result The positive expression rate of β-catenin in gastric cancer tissues was significantly higher than that in normal mucosa tissues, and the positive expression rate of DAB2IP in gastric cancer tissues was significantly lower than that in normal mucosa tissues(P<0.01). The positive expression rate of β-catenin in DAB2IP negative group was significantly higher than that in DAB2IP positive group(P<0.01). Spearman correlation analysis showed that there was a significant negative correlation between DAB2IP and β-catenin expression in gastric cancer tissues(r=-0.535, P<0.01).There were significant differences in the expression of DAB2IP in gastric cancer tissues between patients with different TNM stages, depth of tumor invasion, distant metastases or lymph node metastases(P<0.05). The expression of β-catenin in gastric cancer tissues between patients with different TNM stages, lymph node metastases, differentiation degrees and depth of invasion were significantly different(P<0.05). The survival time of patients in DAB2IP positive expression group was longer than that of patients in DAB2IP negative expression group(P<0.05). Patients in the β-catenin negative expression group had a longer survival time than patients in the positive expression group(P<0.05). Distant metastases and negative expression of DAB2IP were independent risk factors for prognosis in patients with gastric cancer(P<0.01).Conclusion The down-regulation of DAB2IP expression and up-regulation of β-catenin expression in gastric cancer tissues may be effective indicators for the diagnosis and prognosis of gastric cancer, but β-catenin may not be an independent indicator for the prognosis of gastric cancer.
Objective To investigate the expression of disabled homolog 2-interacting protein(DAB2IP) and β-catenin in gastric cancer tissues and its clinical significance. Method Specimens of gastric cancer tissues(n=95) and normal mucosa tissue adjacent to the cancer(n=30) of 95 patients who had undergone radical surgery for gastric cancer were obtained. The expression of DAB2IP and β-catenin was detected by immunohistochemical staining methods between two types of tissue, to analyze the relationship between the positive expression of the above measurements and the clinical features and survival time of the patients. Cox regression model was used to analyze the prognostic factors in patients with gastric cancer. Result The positive expression rate of β-catenin in gastric cancer tissues was significantly higher than that in normal mucosa tissues, and the positive expression rate of DAB2IP in gastric cancer tissues was significantly lower than that in normal mucosa tissues(P<0.01). The positive expression rate of β-catenin in DAB2IP negative group was significantly higher than that in DAB2IP positive group(P<0.01). Spearman correlation analysis showed that there was a significant negative correlation between DAB2IP and β-catenin expression in gastric cancer tissues(r=-0.535, P<0.01).There were significant differences in the expression of DAB2IP in gastric cancer tissues between patients with different TNM stages, depth of tumor invasion, distant metastases or lymph node metastases(P<0.05). The expression of β-catenin in gastric cancer tissues between patients with different TNM stages, lymph node metastases, differentiation degrees and depth of invasion were significantly different(P<0.05). The survival time of patients in DAB2IP positive expression group was longer than that of patients in DAB2IP negative expression group(P<0.05). Patients in the β-catenin negative expression group had a longer survival time than patients in the positive expression group(P<0.05). Distant metastases and negative expression of DAB2IP were independent risk factors for prognosis in patients with gastric cancer(P<0.01).Conclusion The down-regulation of DAB2IP expression and up-regulation of β-catenin expression in gastric cancer tissues may be effective indicators for the diagnosis and prognosis of gastric cancer, but β-catenin may not be an independent indicator for the prognosis of gastric cancer.
引文
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[13]王瀚,牛跃平,董峰,等.不同临床预后患者胃癌组织中DAB2IP表达的差异[J].第三军医大学学报,2016,38(19):2164-2167.
[14]Wlodarczyk J,Rudnicka-Sosin L,Ku?d?a?J.Expression ofβ-catenin and its correlation with metastatic progression of esophagogastric junction adenocarcinoma[J].Pol JPathol,2015,66(4):414-419.
[15]Liu J,Liu L,Wan JX,et al.Long noncoding RNA SN-HG20 promotes gastric cancer progression by inhibiting p21 expression and regulating the GSK-3β/β-catenin signaling pathway[J].Oncotarget,2017,8(46):80700-80708.
[16]Kaya S,Gumus M,Gurbuz Y,et al.The prognostic value ofβ-catenin and LEF-1 expression in patients with operable gastric carcinoma[J].Am J Transl Res,2016,8(2):1228-1236.
[17]陈超,姚莉敏.胃癌中β-catenin、Ki-67和Her-2/Neu表达及对胃癌侵袭、转移的影响[J].重庆医学,2016,45(18):2504-2506.
[18]Wu K,Xie D,Zou Y,et al.The mechanism of DAB2IP in chemoresistance of prostate cancer cells[J].Clin Cancer Res,2013,19(17):4740-4749.
[2]Shimada H,Noie T,Ohashi M,et al.Clinical significance of serum tumor markers for gastric cancer:a systematic review of literature by the task force of the Japanese Gastric Cancer Association[J].Gastric Cancer,2014,17(1):26-33.
[3]Liu L,Xu C,Hsieh JT,et al.DAB2IP in cancer[J].Oncotarget,2016,7(4):3766-3776.
[4]Wu K,Ma L,Zhu J.miR-483-5p promotes growth,invasion and self-renewal of gastric cancer stem cells by Wnt/β-catenin signaling[J].Mol Med Rep,2016,14(4):3421-3428.
[5]Xie D,Gore C,Liu J,et al.Role of DAB2IP in modulating epithelial-to-mesenchymal transition and prostate cancer metastasis[J].Proc Natl Acad Sci U S A,2010,107(6):2485-2490.
[6]朱鹏武,吴春松,郑海红.DAB2IP和β-catenin在胃癌中的表达及其临床意义[J].中国卫生检验杂志,2015,25(15):2545-2547.
[7]Hamilton SR,Aaltonen LA.World Health Organization classification of tumours,pathology and genetics of tumours of digestive system[M].Lyon:IARC Press,2000.
[8]Greene FL,Page DL,Fleming ID,et al.AJCC cancer staging manual[M].6th ed.New York:Springer,2002:136-155.
[9]袁绍萍,温炬,秦思,等.DAB2IP在多种肿瘤中的作用的研究进展[J].广东医学,2018,39(z1):271-273;277.
[10]Xu S,Zhou Y,Du WD,et al.Association of the variant rs2243421 of human DOC-2/DAB2 interactive protein gene(hDAB2IP)with gastric cancer in the Chinese Han population[J].Gene,2013,515(1):200-204.
[11]Tao Y,Sun C,Zhang T,et al.SMURF1 promotes the proliferation,migration and invasion of gastric cancer cells[J].Oncol Rep,2017,38(3):1806-1814.
[12]Dote H,Toyooka S,Tsukuda K,et al.Aberrant promoter methylation in human DAB2 interactive protein(hD-AB2IP)gene in gastrointestinal tumour[J].Br J Cancer,2005,92(6):1117-1125.
[13]王瀚,牛跃平,董峰,等.不同临床预后患者胃癌组织中DAB2IP表达的差异[J].第三军医大学学报,2016,38(19):2164-2167.
[14]Wlodarczyk J,Rudnicka-Sosin L,Ku?d?a?J.Expression ofβ-catenin and its correlation with metastatic progression of esophagogastric junction adenocarcinoma[J].Pol JPathol,2015,66(4):414-419.
[15]Liu J,Liu L,Wan JX,et al.Long noncoding RNA SN-HG20 promotes gastric cancer progression by inhibiting p21 expression and regulating the GSK-3β/β-catenin signaling pathway[J].Oncotarget,2017,8(46):80700-80708.
[16]Kaya S,Gumus M,Gurbuz Y,et al.The prognostic value ofβ-catenin and LEF-1 expression in patients with operable gastric carcinoma[J].Am J Transl Res,2016,8(2):1228-1236.
[17]陈超,姚莉敏.胃癌中β-catenin、Ki-67和Her-2/Neu表达及对胃癌侵袭、转移的影响[J].重庆医学,2016,45(18):2504-2506.
[18]Wu K,Xie D,Zou Y,et al.The mechanism of DAB2IP in chemoresistance of prostate cancer cells[J].Clin Cancer Res,2013,19(17):4740-4749.