AIM: To investigate the expression deficiency of key molecular markers in the homologous recombination pathway. METHODS: Expression loss of breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia mu...AIM: To investigate the expression deficiency of key molecular markers in the homologous recombination pathway. METHODS: Expression loss of breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia mutated (ATM), ATM-Rad3-related (ATR), mediator of DNA damage checkpoint protein 1 (MDC1) and meiotic recombination 11 (Mre11) were correlated with their clinicopathological parameters in gastric cancer (GC). One hundred and twenty treatment-naive GC samples were formalin-fixed and paraffin-embedded into tissue blocks. Two representative cores from each block were extracted and constructed into tissue microarrays. Expression levels of BRCA1, ATM, ATR, MDC1 and Mre11 were determined using immunohistochemical analysis, and correlated with clinical parameters, including age, gender, Lauren subtype, tumor grades, clinical stage and overall survival.RESULTS: Expression loss of BRCA1, ATM, ATR, MDC1, and Mre11 was found in 21.4%, 20.2%, 21.0%, 11.1% and 4.6%, respectively, of interpretable cases. BRCA1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 8.2% vs 31.7%, P = 0.001), higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 10.7% vs 20.5;Ⅰ/Ⅱ vs Ⅳ, 10.7% vs 54.5%, P = 0.047) and advanced clinical stage (Ⅰ/Ⅱ vs Ⅲ, 12.9% vs 16.9%;Ⅰ /Ⅱ vs Ⅳ, 12.9% vs 45.5%, P = 0.006). MDC1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 0% vs 19.7%, P = 0.001) and higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 0% vs 12%;Ⅰ/Ⅱ vs Ⅳ, 0% vs 30.8%, P = 0.012). In addition, the survival time of the patients with expression loss of BRCA1 was significantly shorter than those with positive expression of BRCA1 (2-year survival rate, 32.4% vs 62.8%, P = 0.015). No correlations were found between clinicopathological parameters and expression loss of ATM, ATR and Mre11. CONCLUSION: Our results support the hypothesis that homologous recombination deficiency plays an important role in the progression of gastric carcinoma. Loss of expression of BRCA1 and MDC1 may serve as predictive factors in tumor development or progression in GC patients.展开更多
目的探讨miR-590-5p、DNA损伤检查点蛋白调节子1(mediator of DNA damage checkpoint 1,MDC1)在高级别胶质瘤(high-grade glioma,HGG)组织中的表达及与胶质瘤病人术后放疗效果的关系,并明确二者对胶质瘤细胞增殖、凋亡的影响。方法选取2...目的探讨miR-590-5p、DNA损伤检查点蛋白调节子1(mediator of DNA damage checkpoint 1,MDC1)在高级别胶质瘤(high-grade glioma,HGG)组织中的表达及与胶质瘤病人术后放疗效果的关系,并明确二者对胶质瘤细胞增殖、凋亡的影响。方法选取2019年1月至2021年2月河北北方学院附属第一医院64例HGG患者,评估放疗效果。实时荧光定量PCR(qRT-PCR)法检测miR-590-5p水平,免疫组织化学染色检测MDC1表达情况,分析miR-590-5p、MDC1表达与胶质瘤病人术后放疗效果的关系,多因素Logistic回归分析影响HGG患者术后放疗效果的因素;体外培养胶质瘤U87MG细胞,并分别转染miR-590-5p mimic、MDC1-shRNA及其阴性对照,CCK-8法和流式细胞术分别检测细胞增殖和凋亡;构建裸鼠移植瘤模型,观察过表达miR-590-5p和敲低MDC1对肿瘤生长的影响。结果MDC1在HGG组织中的表达较正常脑组织中升高,mi R-590-5p表达较正常脑组织降低,二者表达水平呈负相关;MDC1表达升高、miR-590-5p表达降低,其放疗效果越差;Logistic回归分析显示,MDC1高表达、miR-590-5p低表达均是影响HGG患者放疗效果的危险因素。过表达miR-590-5p和敲低MDC1后,U87MG细胞增殖力降低,凋亡率升高,移植瘤体积和重量下降,Ki-67阳性细胞比例减少。过表达miR-590-5p后MDC1蛋白表达明显下降。结论HGG组织中miR-590-5p呈低表达,MDC1呈高表达,二者表达与HGG的发生和患者术后放疗效果关系密切;过表达miR-590-5p和敲低MDC1表达可抑制胶质瘤细胞增殖并促进凋亡。展开更多
文摘AIM: To investigate the expression deficiency of key molecular markers in the homologous recombination pathway. METHODS: Expression loss of breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia mutated (ATM), ATM-Rad3-related (ATR), mediator of DNA damage checkpoint protein 1 (MDC1) and meiotic recombination 11 (Mre11) were correlated with their clinicopathological parameters in gastric cancer (GC). One hundred and twenty treatment-naive GC samples were formalin-fixed and paraffin-embedded into tissue blocks. Two representative cores from each block were extracted and constructed into tissue microarrays. Expression levels of BRCA1, ATM, ATR, MDC1 and Mre11 were determined using immunohistochemical analysis, and correlated with clinical parameters, including age, gender, Lauren subtype, tumor grades, clinical stage and overall survival.RESULTS: Expression loss of BRCA1, ATM, ATR, MDC1, and Mre11 was found in 21.4%, 20.2%, 21.0%, 11.1% and 4.6%, respectively, of interpretable cases. BRCA1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 8.2% vs 31.7%, P = 0.001), higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 10.7% vs 20.5;Ⅰ/Ⅱ vs Ⅳ, 10.7% vs 54.5%, P = 0.047) and advanced clinical stage (Ⅰ/Ⅱ vs Ⅲ, 12.9% vs 16.9%;Ⅰ /Ⅱ vs Ⅳ, 12.9% vs 45.5%, P = 0.006). MDC1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 0% vs 19.7%, P = 0.001) and higher tumor grade (Ⅰ/Ⅱ vs Ⅲ, 0% vs 12%;Ⅰ/Ⅱ vs Ⅳ, 0% vs 30.8%, P = 0.012). In addition, the survival time of the patients with expression loss of BRCA1 was significantly shorter than those with positive expression of BRCA1 (2-year survival rate, 32.4% vs 62.8%, P = 0.015). No correlations were found between clinicopathological parameters and expression loss of ATM, ATR and Mre11. CONCLUSION: Our results support the hypothesis that homologous recombination deficiency plays an important role in the progression of gastric carcinoma. Loss of expression of BRCA1 and MDC1 may serve as predictive factors in tumor development or progression in GC patients.
文摘目的探讨miR-590-5p、DNA损伤检查点蛋白调节子1(mediator of DNA damage checkpoint 1,MDC1)在高级别胶质瘤(high-grade glioma,HGG)组织中的表达及与胶质瘤病人术后放疗效果的关系,并明确二者对胶质瘤细胞增殖、凋亡的影响。方法选取2019年1月至2021年2月河北北方学院附属第一医院64例HGG患者,评估放疗效果。实时荧光定量PCR(qRT-PCR)法检测miR-590-5p水平,免疫组织化学染色检测MDC1表达情况,分析miR-590-5p、MDC1表达与胶质瘤病人术后放疗效果的关系,多因素Logistic回归分析影响HGG患者术后放疗效果的因素;体外培养胶质瘤U87MG细胞,并分别转染miR-590-5p mimic、MDC1-shRNA及其阴性对照,CCK-8法和流式细胞术分别检测细胞增殖和凋亡;构建裸鼠移植瘤模型,观察过表达miR-590-5p和敲低MDC1对肿瘤生长的影响。结果MDC1在HGG组织中的表达较正常脑组织中升高,mi R-590-5p表达较正常脑组织降低,二者表达水平呈负相关;MDC1表达升高、miR-590-5p表达降低,其放疗效果越差;Logistic回归分析显示,MDC1高表达、miR-590-5p低表达均是影响HGG患者放疗效果的危险因素。过表达miR-590-5p和敲低MDC1后,U87MG细胞增殖力降低,凋亡率升高,移植瘤体积和重量下降,Ki-67阳性细胞比例减少。过表达miR-590-5p后MDC1蛋白表达明显下降。结论HGG组织中miR-590-5p呈低表达,MDC1呈高表达,二者表达与HGG的发生和患者术后放疗效果关系密切;过表达miR-590-5p和敲低MDC1表达可抑制胶质瘤细胞增殖并促进凋亡。
