Background T-lymphoma and metastasis gene 1 （Tiaml） produces a guanine nucleotide exchange factor （GNEF） that regulates guanosine triphosphatase, which transforms guanosine diphosphate to guanosine triphosphate. R...Background T-lymphoma and metastasis gene 1 （Tiaml） produces a guanine nucleotide exchange factor （GNEF） that regulates guanosine triphosphatase, which transforms guanosine diphosphate to guanosine triphosphate. Recently published data indicate that Tiaml was associated with gastric cancer. The aim of this study was to investigate biological effects and potential mechanisms of Tiara1 in gastric carcinoma. Methods We analyzed the expression of Tiaml in 114 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time PCR. We investigated Tiaml expression and its prognostic value for gastric cancer. Furthermore, the functions of Tiaml over-expression were analyzed with stable-expression Tiara1 plasmid in human gastric cancer cell lines. Results Tiaml expression was significantly associated with cell differentiation and lymphatic metastasis; expression of Tiaml mRNA was up-regulated in gastric cancer compared to pair-matched adjacent non-tumor tissues. Analyses of surgical tissue samples and 5-year survival of gastric cancer patients showed that those with strong Tiaml expression had significantly shorter overall survival time than those with negative Tiaml expression. Ectopic expression of Tiaml promoted cell growth, migration and invasion of gastric cancer cells in vitro. Conclusions In gastric cancer cells, Tiaml affects multiple properties associated with acquisition of the metastatic phenotype, and may be a marker of gastric cancer progression and metastasis in a subset of cancer.展开更多
目的探讨T淋巴瘤侵袭转移诱导因子1(Tiam1)在子宫颈癌组织中表达及意义。方法留取子宫颈癌组织84例,宫颈上皮内瘤变(CIN)组织56例,留取子宫良性病变患者正常宫颈组织43例,利用实时荧光定量PCR技术检测不同组织中Tiam1基因表达,利用免疫...目的探讨T淋巴瘤侵袭转移诱导因子1(Tiam1)在子宫颈癌组织中表达及意义。方法留取子宫颈癌组织84例,宫颈上皮内瘤变(CIN)组织56例,留取子宫良性病变患者正常宫颈组织43例,利用实时荧光定量PCR技术检测不同组织中Tiam1基因表达,利用免疫组织化学法检测不同组织中Tiam1蛋白表达。结果子宫颈癌组织中Tiam1 m RNA相对表达量和蛋白阳性表达率[(2.05±0.17)%和82.1%]均高于CIN组织[(1.74±0.24)%和46.4%]和正常宫颈组织[(1.27±0.16)%和14.0%],且CIN组织高于正常宫颈组织(P<0.001),CINⅠ组织中Tiam1 m RNA相对表达量(1.54±0.19)显著低于CINⅡ~Ⅲ组织(1.81±0.23),差异有统计学意义(t=22.186,P=0.016),即子宫颈癌组织>CINⅡ~Ⅲ组织>CINⅠ组织>正常宫颈组织;子宫颈癌组织中Tiam1 m RNA相对表达量和蛋白阳性表达率均与临床分期、病理分级、浸润深度、淋巴结转移有关(P<0.05);Kaplan-Meier生存分析结果显示,高表达组患者生存时间44.13个月,低表达组患者生存时间61.00个月,Tiam1蛋白阳性表达患者生存时间34.67个月,阴性表达患者生存时间63.76个月,Log-Rank检验显示均差异有统计学意义(均P<0.05);Cox比例风险回归模型分析结果显示,临床分期、淋巴结转移和Tiam1表达是患者预后的影响因素(均P<0.05)。结论Tiam1基因和蛋白在子宫颈癌组织中呈高表达,且与患者预后密切相关,有望成为预测患者预后的有效分子指标。展开更多
基金This study was supported by a grant from the Natural Science Foundation of Shandong Province of China （Nos. ZR2011HM041, Y2007C102, ZR2011HM076）, Key Research Project from Shandong Science and Technology Commission （Nos. 2011GGH21844, 2007H2071）, and the the National Youthful Science Foundation of China （No. 81101858）.
文摘Background T-lymphoma and metastasis gene 1 （Tiaml） produces a guanine nucleotide exchange factor （GNEF） that regulates guanosine triphosphatase, which transforms guanosine diphosphate to guanosine triphosphate. Recently published data indicate that Tiaml was associated with gastric cancer. The aim of this study was to investigate biological effects and potential mechanisms of Tiara1 in gastric carcinoma. Methods We analyzed the expression of Tiaml in 114 pair-matched gastric neoplastic and adjacent non-neoplastic tissues by quantitative real-time PCR. We investigated Tiaml expression and its prognostic value for gastric cancer. Furthermore, the functions of Tiaml over-expression were analyzed with stable-expression Tiara1 plasmid in human gastric cancer cell lines. Results Tiaml expression was significantly associated with cell differentiation and lymphatic metastasis; expression of Tiaml mRNA was up-regulated in gastric cancer compared to pair-matched adjacent non-tumor tissues. Analyses of surgical tissue samples and 5-year survival of gastric cancer patients showed that those with strong Tiaml expression had significantly shorter overall survival time than those with negative Tiaml expression. Ectopic expression of Tiaml promoted cell growth, migration and invasion of gastric cancer cells in vitro. Conclusions In gastric cancer cells, Tiaml affects multiple properties associated with acquisition of the metastatic phenotype, and may be a marker of gastric cancer progression and metastasis in a subset of cancer.
文摘目的探讨T淋巴瘤侵袭转移诱导因子1(Tiam1)在子宫颈癌组织中表达及意义。方法留取子宫颈癌组织84例,宫颈上皮内瘤变(CIN)组织56例,留取子宫良性病变患者正常宫颈组织43例,利用实时荧光定量PCR技术检测不同组织中Tiam1基因表达,利用免疫组织化学法检测不同组织中Tiam1蛋白表达。结果子宫颈癌组织中Tiam1 m RNA相对表达量和蛋白阳性表达率[(2.05±0.17)%和82.1%]均高于CIN组织[(1.74±0.24)%和46.4%]和正常宫颈组织[(1.27±0.16)%和14.0%],且CIN组织高于正常宫颈组织(P<0.001),CINⅠ组织中Tiam1 m RNA相对表达量(1.54±0.19)显著低于CINⅡ~Ⅲ组织(1.81±0.23),差异有统计学意义(t=22.186,P=0.016),即子宫颈癌组织>CINⅡ~Ⅲ组织>CINⅠ组织>正常宫颈组织;子宫颈癌组织中Tiam1 m RNA相对表达量和蛋白阳性表达率均与临床分期、病理分级、浸润深度、淋巴结转移有关(P<0.05);Kaplan-Meier生存分析结果显示,高表达组患者生存时间44.13个月,低表达组患者生存时间61.00个月,Tiam1蛋白阳性表达患者生存时间34.67个月,阴性表达患者生存时间63.76个月,Log-Rank检验显示均差异有统计学意义(均P<0.05);Cox比例风险回归模型分析结果显示,临床分期、淋巴结转移和Tiam1表达是患者预后的影响因素(均P<0.05)。结论Tiam1基因和蛋白在子宫颈癌组织中呈高表达,且与患者预后密切相关,有望成为预测患者预后的有效分子指标。
