目的探讨m^(6)A去甲基化酶烷基化修复蛋白B同源物5(alkylation repair protein B homolog 5,ALKHB5)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法收集2009年1月至2013年8月在桂林医学院附属医院接受肝癌切...目的探讨m^(6)A去甲基化酶烷基化修复蛋白B同源物5(alkylation repair protein B homolog 5,ALKHB5)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法收集2009年1月至2013年8月在桂林医学院附属医院接受肝癌切除术的80例HCC患者的癌组织及其癌旁组织(距病灶>3 cm)的石蜡包埋标本,采用免疫组化法检测ALKBH5的表达水平,并分析其与HCC患者临床病理特征及与预后的关系。结果在HCC组织中ALKBH5高表达的患者比例明显低于癌旁组织(P=0.001),且与肿瘤大小和血清甲胎蛋白(α⁃fetoprotein,AFP)水平相关(均P<0.05)。Kaplan⁃Meier生存分析显示ALKBH5低表达组患者的总生存期(P=0.011)和无复发生存期(P=0.012)均缩短,多因素Cox回归分析显示ALKBH5低表达是影响HCC患者总生存期(HR=1.965,95%CI:1.029~3.751,P=0.041)和无复发生存期(HR=2.201,95%CI:1.046~4.629,P=0.038)的独立危险因素。结论ALKBH5在HCC组织中表达下调且低表达患者预后不良,ALKBH5可能是HCC潜在的预后评估指标及治疗靶点。展开更多
AIM: To determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis.METHODS: The Ku70/80 DNA-binding activity was ...AIM: To determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis.METHODS: The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot analysis.RESULTS: A statistically significant difference was found in both adenomas and carcinomas as compared to matched normal colonic mucosa (P＜0.00). However,changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the activity.Tumors, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86nuclear expression, as determined by Western blot and immunohistochemical analyses (P＜0.001). Cytoplasmic protein expression was found in pathological samples,but not in normal tissues either from tumor patients or from healthy subjects.CONCLUSION: Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis.展开更多
目的分析淋巴结转移性结直肠癌中DNA错配修复基因(mismatch repair,MMR)系统MLH1(Mut L homolog1)和MSH2(Mut S homolog 2)基因的表达水平及临床意义。方法选取2015年6月至2017年4月收治的120例淋巴结转移性结直肠癌患者为研究对象,同...目的分析淋巴结转移性结直肠癌中DNA错配修复基因(mismatch repair,MMR)系统MLH1(Mut L homolog1)和MSH2(Mut S homolog 2)基因的表达水平及临床意义。方法选取2015年6月至2017年4月收治的120例淋巴结转移性结直肠癌患者为研究对象,同期选取120例无淋巴结转移的结直肠癌患者为对照;通过免疫组化法、实时荧光定量PCR法(q RT-PCR)、Western blot法,分别检测两组正常癌旁组织及病灶组织中MLH1、MSH2蛋白阳性表达缺失率,MLH1、MSH2 m RNA及蛋白表达水平。结果两组患者病灶组织MLH1、MSH2蛋白阳性表达缺失率均高于癌旁组织,而MLH1、MSH2 m RNA及蛋白相对表达水平均低于癌旁组织,差异均有统计学意义(P均<0.05);淋巴结转移性结直肠癌组病灶组织MLH1、MSH2蛋白阳性表达缺失率均高于无淋巴结转移组,MLH1、MSH2 m RNA及蛋白相对表达水平均低于无淋巴结转移组,差异均有统计学意义(P均<0.05);两组癌旁组织MLH1、MSH2蛋白阳性表达缺失率、MLH1、MSH2 m RNA及蛋白相对表达水平比较差异均无统计学意义(P均>0.05);MLH1、MSH阳性表达缺失率与淋巴结转移性结直肠癌患者的肿瘤直径、浸润深度、分化程度及淋巴结转移数有密切关系(P均<0.01),而与年龄无关(P>0.05)。结论淋巴结转移性结直肠癌中MLH1、MSH2表达水平显著降低,推测其在结直肠癌由无淋巴结转移进展为发生淋巴结转移中具有重要作用。展开更多
文摘目的探讨m^(6)A去甲基化酶烷基化修复蛋白B同源物5(alkylation repair protein B homolog 5,ALKHB5)在肝细胞癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法收集2009年1月至2013年8月在桂林医学院附属医院接受肝癌切除术的80例HCC患者的癌组织及其癌旁组织(距病灶>3 cm)的石蜡包埋标本,采用免疫组化法检测ALKBH5的表达水平,并分析其与HCC患者临床病理特征及与预后的关系。结果在HCC组织中ALKBH5高表达的患者比例明显低于癌旁组织(P=0.001),且与肿瘤大小和血清甲胎蛋白(α⁃fetoprotein,AFP)水平相关(均P<0.05)。Kaplan⁃Meier生存分析显示ALKBH5低表达组患者的总生存期(P=0.011)和无复发生存期(P=0.012)均缩短,多因素Cox回归分析显示ALKBH5低表达是影响HCC患者总生存期(HR=1.965,95%CI:1.029~3.751,P=0.041)和无复发生存期(HR=2.201,95%CI:1.046~4.629,P=0.038)的独立危险因素。结论ALKBH5在HCC组织中表达下调且低表达患者预后不良,ALKBH5可能是HCC潜在的预后评估指标及治疗靶点。
基金Supported by Italian Ministero della Salute, IRCCS, RC0302TG13 by Ministero dell'Istruzíone, Università e Ricerca scientifica e tecnologica (MIUR), COFIN2002, to the Universita Campus Bio-Medico
文摘AIM: To determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis.METHODS: The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot analysis.RESULTS: A statistically significant difference was found in both adenomas and carcinomas as compared to matched normal colonic mucosa (P＜0.00). However,changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the activity.Tumors, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86nuclear expression, as determined by Western blot and immunohistochemical analyses (P＜0.001). Cytoplasmic protein expression was found in pathological samples,but not in normal tissues either from tumor patients or from healthy subjects.CONCLUSION: Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis.
文摘目的分析淋巴结转移性结直肠癌中DNA错配修复基因(mismatch repair,MMR)系统MLH1(Mut L homolog1)和MSH2(Mut S homolog 2)基因的表达水平及临床意义。方法选取2015年6月至2017年4月收治的120例淋巴结转移性结直肠癌患者为研究对象,同期选取120例无淋巴结转移的结直肠癌患者为对照;通过免疫组化法、实时荧光定量PCR法(q RT-PCR)、Western blot法,分别检测两组正常癌旁组织及病灶组织中MLH1、MSH2蛋白阳性表达缺失率,MLH1、MSH2 m RNA及蛋白表达水平。结果两组患者病灶组织MLH1、MSH2蛋白阳性表达缺失率均高于癌旁组织,而MLH1、MSH2 m RNA及蛋白相对表达水平均低于癌旁组织,差异均有统计学意义(P均<0.05);淋巴结转移性结直肠癌组病灶组织MLH1、MSH2蛋白阳性表达缺失率均高于无淋巴结转移组,MLH1、MSH2 m RNA及蛋白相对表达水平均低于无淋巴结转移组,差异均有统计学意义(P均<0.05);两组癌旁组织MLH1、MSH2蛋白阳性表达缺失率、MLH1、MSH2 m RNA及蛋白相对表达水平比较差异均无统计学意义(P均>0.05);MLH1、MSH阳性表达缺失率与淋巴结转移性结直肠癌患者的肿瘤直径、浸润深度、分化程度及淋巴结转移数有密切关系(P均<0.01),而与年龄无关(P>0.05)。结论淋巴结转移性结直肠癌中MLH1、MSH2表达水平显著降低,推测其在结直肠癌由无淋巴结转移进展为发生淋巴结转移中具有重要作用。
