基础转录激活因子1蛋白在胃癌组织中的表达及其临床意义
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摘要
目的:探讨基础转录激活因子1 (ABT1)蛋白在胃癌组织中的表达及其与胃癌患者临床参数和预后的相关性,阐明ABT1在胃癌发生发展中的作用。方法:选择100例胃癌患者的胃癌组织和80例与其配对的癌旁组织,采用免疫组织化学法检测ABT1蛋白在癌组织及癌旁组织中的表达情况。对免疫组织化学结果中染色细胞的比例和染色程度进行半定量分析,对半定量分析结果与胃癌患者临床参数的关系进行统计学分析。采用Kaplan-Meier法分析ABT1蛋白表达水平与胃癌患者生存期的相关性。结果:ABT1蛋白在胃癌组织和癌旁组织中的细胞核和细胞质中均有表达,且胃癌组织中ABT1蛋白表达水平低于癌旁组织(P=0.021);胃癌患者胃癌组织中ABT1蛋白表达水平与胃癌组织病理分级呈负相关关系(r=-0.224,P=0.026)。Kaplan-Meier生存曲线分析,胃癌患者ABT1蛋白高表达与预后良好呈正相关关系(HR=1.483,P<0.01),且ABT1蛋白高表达的胃癌患者生存率明显高于ABT1蛋白低表达的胃癌患者(HR=2.411,P=0.027)。结论:ABT1蛋白在胃癌组织中低表达,提示其可作为胃癌预后良好的标志因子之一。
Objective:To investigate the expression of activator of basal transcription 1(ABT1)protein in gastric cancer tissue and its relationships with the clinical parameters and prognosis of gastric cancer patients,and to clarify the role of ABT1 in the occurrence and development of gastric cancer.Methods:A total of 100 cases of cancer tissue of the gastric cancer patients and 80 pairs of adjacent tissue were selected.The expressions of ABT1 in cancer tissue and adjacent tissue were detected by immunohistochemistry and the proportion of stained cells and the degree of staining in the immunohistochemistry results were analyzed using semi-quantitative analysis.The relationships between the semi-quantitative analysis results and the clinical parameters of gastric cancer patients were statistically analyzed.Kaplan-Meier method was used to analyze the correlation between the ABT1 protein expression level and the survival of gastric cancer patients.Results:ABT1-positive staining was observed in the nucleus and cytoplasm of gastric cancer tissue and adjacent gastric tissue.The expression level of ABT1 in gastric cancer tissue was lower than that in adjacent tissue(P=0.021).The ABT1 protein expression level in gastric cancer tissue was significantly negatively correlated with the pathological grade(r=-0.224,P=0.026).The Kaplan-Meier analysis results of the survival curve showed that the high expression of ABT1 was associated with good prognosis in the gastric cancer patients(HR=1.483,P<0.01).The survival rate of gastric cancer patients with high ABT1 expression was significantly higher than that of the patients with low ABT1 expression(HR=2.411,P=0.0272).Conclusion:The expression of ABT1 in gastric cancer tissue is lower,indicating that ABT1 can be used one of the markers of good prognosis of gastric cancer.
Objective:To investigate the expression of activator of basal transcription 1(ABT1)protein in gastric cancer tissue and its relationships with the clinical parameters and prognosis of gastric cancer patients,and to clarify the role of ABT1 in the occurrence and development of gastric cancer.Methods:A total of 100 cases of cancer tissue of the gastric cancer patients and 80 pairs of adjacent tissue were selected.The expressions of ABT1 in cancer tissue and adjacent tissue were detected by immunohistochemistry and the proportion of stained cells and the degree of staining in the immunohistochemistry results were analyzed using semi-quantitative analysis.The relationships between the semi-quantitative analysis results and the clinical parameters of gastric cancer patients were statistically analyzed.Kaplan-Meier method was used to analyze the correlation between the ABT1 protein expression level and the survival of gastric cancer patients.Results:ABT1-positive staining was observed in the nucleus and cytoplasm of gastric cancer tissue and adjacent gastric tissue.The expression level of ABT1 in gastric cancer tissue was lower than that in adjacent tissue(P=0.021).The ABT1 protein expression level in gastric cancer tissue was significantly negatively correlated with the pathological grade(r=-0.224,P=0.026).The Kaplan-Meier analysis results of the survival curve showed that the high expression of ABT1 was associated with good prognosis in the gastric cancer patients(HR=1.483,P<0.01).The survival rate of gastric cancer patients with high ABT1 expression was significantly higher than that of the patients with low ABT1 expression(HR=2.411,P=0.0272).Conclusion:The expression of ABT1 in gastric cancer tissue is lower,indicating that ABT1 can be used one of the markers of good prognosis of gastric cancer.
引文
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[3]RAVARANI C H,CHALANCON G,BREKER M,et al.Affinity and competition for TBP are molecular determinants of gene expression noise[J].Nat Commun,2016,7:10417.
[4]ARKOVA O,KUZNETSOV N,FEDOROVA O,et al.Areal-time study of the interaction of TBP with a TATA boxcontaining duplex identical to an ancestral or minor allele of human gene LEP or TPI[J].J Biomol Struct Dyn,2016,35(14):3070-3081.
[5]MAEDA R,TAMASHIRO H,TAKANO K,et al.TBP-like protein(TLP)disrupts the p53-MDM2interaction and induces long-lasting p53activation[J].J Biol Chem,2017,292(8):3201-3212.
[6]LOMVARDAS S,THANOS D.Nucleosome sliding via TBPDNA binding in vivo[J].Cell,2001,106(6):685-696.
[7]CHEN D,HINKLEY C S,HENRY RW,et al.TBPdynamics in living human cells:constitutive association of TBPwith mitotic chromosomes[J].Mol Biol Cell,2002,13(1):276-284.
[8]TORA L.A unified nomenclature for TATA box binding protein(TBP)-associated factors(TAFs)involved in RNApolymerase II transcription[J].Genes Dev,2002,16(6):673-675.
[9]ODA T,FUKUDA A,HAGIWARA H,et al.ABT1-associated protein(ABTAP),a novel nuclear protein conserved from yeast to mammals,represses transcriptional activation by ABT1[J].J Cell Biochem,2004,93(4):788-806.
[10]JOHNSON S A S,LIN J J,WALKEY C J,et al.Elevated TATA-binding protein expression drives vascular endothelial growth factor expression in colon cancer[J].Oncotarget,2017,8(30):48832-48845.
[11]YAN J,WEI Q,JIAN W,et al.IMP3predicts invasion and prognosis in human lung adenocarcinoma[J].Lung,2016,194(1):137-146.
[12]CHEN W,GUO W,LI M,et al.Upregulation of cleavage and polyadenylation specific factor 4in lung adenocarcinoma and its critical role for cancer cell survival and proliferation[J].PLoS ONE,2013,8(12):e82728.
[13]KIM H Y,CHO Y,KANG H,et al.Targeting the WEE1kinase as a molecular targeted therapy for gastric cancer[J].Oncotarget,2016,7(31):49902-49916.
[14]KIM S J,HWANG J A,RO J Y,et al.Galectin-7is epigenetically-regulated tumor suppressor in gastric cancer[J].Oncotarget,2013,4(9):1461-1471.
[15]GARATTINI S K,BASILE D,CATTANEO M,et al.Molecular classifications of gastric cancers:Novel insights and possible future applications[J].World J Gastrointest Oncol,2017,9(5):194-208.
[16]WANG Z,LIU C.Lgr5-positive cells are cancer-stem-celllike cells in gastric cancer[J].Cell Physiol Biochem,2015,36(6):2447-2455.
[17]LI Y,YANG X,WU Y,et al.B7-H3promotes gastric cancer cell migration and invasion[J].Oncotarget,2017,8(42):71725-71735.
[18]ZHOU Y,ZHANG G J,WANG J,et al.Current status of lymph node micrometastasis in gastric cancer[J].Oncotarget,2017,8(31):51963-51969.
[19]EGELAND E V,FLATMARK K,NESLAND J M,et al.Expression and clinical significance of Wee1 in colorectal cancer[J].Tumour Biol,2016,37(9):12133-12140.
[20]CRIGHTON D,WOIWODE A,ZHANG C,et al.p53represses RNA polymeraseⅢtranscription by targeting TBPand inhibiting promoter occupancy by TFⅢB[J].EMBO J,2003,22(11):2810-2820.
[21]SZSZ A M,LNCZKY A,NAGY,et al.Crossvalidation of survival associated biomarkers in gastric cancer using transcriptomic data of 1 065patients[J].Oncotarget,2016,7(31):49322-49333.