目的研究DNA修复基因切除修复交叉互补组1(resection and repair of cross-complementary group 1,ERCC1)在乳腺癌组织中的表达情况以及对术后远处转移的影响,为乳腺癌患者预后判断和治疗靶点筛选提供参考。方法采用前瞻性巢式病例对照...目的研究DNA修复基因切除修复交叉互补组1(resection and repair of cross-complementary group 1,ERCC1)在乳腺癌组织中的表达情况以及对术后远处转移的影响,为乳腺癌患者预后判断和治疗靶点筛选提供参考。方法采用前瞻性巢式病例对照研究,病例选自2013年西南医科大学附属医院建立的乳腺癌队列,按照患者年龄、手术时间、手术方式、化疗方案等重要治疗方案进行1:1匹配,根据术后是否发生远处转移分转移组(93例)和未转移组(93例),通过免疫组化检查分析ERCC1在转移组和未转移组中的表达差异,通过R语言绘制ROC曲线并获得最佳截断值,SPSS软件进行比例风险(Cox)回归模型分析进而探讨ERCC1对患者术后转移的作用。结果两组乳腺癌患者孕激素受体状态和淋巴结转移数目有统计学差异(P<0.05),而其他临床病理特征无统计学意义(P>0.05)。ERCC1主要分布在乳腺癌细胞的细胞核中,阳性表达为棕黄色颗粒;ERCC1在转移组患者的蛋白表达高于对照组(P<0.05)。ERCC1是乳腺癌转移的危险因素(HR=1.155,95%CI:1.007~1.323,P=0.039)。ROC曲线最佳截断值为1.5,将患者分为ERCC1高表达组和低表达组,高表达组发生转移的风险是低表达组的5.327倍(HR=5.327,95%CI:1.894~14.988,P=0.002)。结论ERCC1是乳腺癌患者术后转移的危险因素,可作为预后评估的潜在生物标志物和治疗靶点。展开更多
Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damag...Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.展开更多
文摘目的研究DNA修复基因切除修复交叉互补组1(resection and repair of cross-complementary group 1,ERCC1)在乳腺癌组织中的表达情况以及对术后远处转移的影响,为乳腺癌患者预后判断和治疗靶点筛选提供参考。方法采用前瞻性巢式病例对照研究,病例选自2013年西南医科大学附属医院建立的乳腺癌队列,按照患者年龄、手术时间、手术方式、化疗方案等重要治疗方案进行1:1匹配,根据术后是否发生远处转移分转移组(93例)和未转移组(93例),通过免疫组化检查分析ERCC1在转移组和未转移组中的表达差异,通过R语言绘制ROC曲线并获得最佳截断值,SPSS软件进行比例风险(Cox)回归模型分析进而探讨ERCC1对患者术后转移的作用。结果两组乳腺癌患者孕激素受体状态和淋巴结转移数目有统计学差异(P<0.05),而其他临床病理特征无统计学意义(P>0.05)。ERCC1主要分布在乳腺癌细胞的细胞核中,阳性表达为棕黄色颗粒;ERCC1在转移组患者的蛋白表达高于对照组(P<0.05)。ERCC1是乳腺癌转移的危险因素(HR=1.155,95%CI:1.007~1.323,P=0.039)。ROC曲线最佳截断值为1.5,将患者分为ERCC1高表达组和低表达组,高表达组发生转移的风险是低表达组的5.327倍(HR=5.327,95%CI:1.894~14.988,P=0.002)。结论ERCC1是乳腺癌患者术后转移的危险因素,可作为预后评估的潜在生物标志物和治疗靶点。
文摘Background:Platinum chemotherapy(CT)remains the backbone of systemic therapy for patients with smallcell lung cancer(SCLC).The nucleotide excision repair(NER)pathway plays a central role in the repair of the DNA damage exerted by platinum agents.Alteration in this repair mechanism may affect patients’survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease(ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit,Careggi University Hospital,Florence(Italy),from 2015 to 2020.mRNA expression analysis and single nucleotide polymorphism(SNP)characterization of three NER pathway genes—namely ERCC1,ERCC2,and ERCC5—were performed on patient tumor samples.Results:Overall,elevated expression of ERCC genes was observed in SCLC patients compared to healthy controls.Patients with low ERCC1 and ERCC5 expression levels exhibited a better median progression-free survival(mPFS=7.1 vs.4.9 months,p=0.39 for ERCC1 and mPFS=6.9 vs.4.8 months,p=0.093 for ERCC5)and overall survival(mOS=8.7 vs.6.0 months,p=0.4 for ERCC1 and mOS=7.2 vs.6.2 months,p=0.13 for ERCC5).Genotyping analysis of five SNPs of ERCC genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the ERCC1 rs11615 SNP(p=0.24 for PFS and p=0.14 for OS)and of the rs13181 and rs1799793 ERCC2 SNPs(p=0.43 and p=0.26 for PFS and p=0.21 and p=0.16 for OS,respectively)compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of ERCC gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.
