Emodin regulating excision repair cross-complementation group 1 through fibroblast growth factor receptor 2 signaling

AIM: To investigate the molecular mechanisms underlying the reversal effect of emodin on platinum resistance in hepatocellular carcinoma. METHODS: After the addition of 10 μmol/L emodin to HepG2/oxaliplatin (OXA) cells, the inhibition rate (IR), 50% inhibitory concentration (IC 50 ) and reversal index (IC 50 in experimental group/IC 50 in control group) were calculated. For HepG2, HepG2/OXA, HepG2/OXA/T, each cell line was divided into a control group, OXA group, OXA + fibroblast growth factor 7 (FGF7) group and OXA + emodin group, and the final concentrations of FGF7, emodin and OXA in each group were 5 ng/mL, 10 μg/mL and 10 μmol/L, respectively. Single-cell gel electrophoresis was conducted to detect DNA damage, and the fibroblast growth factor receptor 2 (FGFR2), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and excision repair cross-complementing gene 1 (ERCC1) protein expression levels in each group were examined by Western blotting. RESULTS: Compared with the IC50 of 120.78 μmol/L in HepG2/OXA cells, the IC 50 decreased to 39.65 μmol/L after treatment with 10 μmol/L emodin; thus, the reversal index was 3.05. Compared with the control group, the tail length and Olive tail length in the OXA group, OXA + FGF7 group and OXA + emodin group were significantly increased, and the differences were statistically significant (P < 0.01). The tail length and Olive tail length were lower in the OXA + FGF7 group than in the OXA group, and this difference was also statistically significant. Compared with the OXA + FGF7 group, the tail extent, the Olive tail moment and the percentage of tail DNA were significantly increased in the OXA + emodin group, and these differences were statistically significant (P < 0.01). In comparison with its parental cell line HepG2, the HepG2/OXA cells demonstrated significantly increased FGFR2, p-ERK1/2 and ERCC1 expression levels, whereas the expression of all three molecules was significantly inhibited in HepG2/ OXA/T cells, in which FGFR2 was silenced by FGFR2 shRNA. In the examined HepG2 cells, the FGFR2, p-ERK1/2 and ERCC1 expression levels demonstrated increasing trends in the OXA group and OXA + FGF7 group. Compared with the OXA group and OXA + FGF7 group, the FGFR2, p-ERK1/2, and ERCC1 expression levels were significantly lower in the OXA + emodin group, and these differences were statistically significant. In the HepG2/OXA/T cell line that was transfected with FGFR2 shRNA, the FGFR2, p-ERK1/2 and ERCC1 expression levels were significantly inhibited, but there were no significant differences in these expression levels among the OXA, OXA + FGF7 and OXA + emodin groups. CONCLUSION: Emodin markedly reversed OXA resistance by enhancing OXA DNA damage in HepG2/OXA cells, and the molecular mechanism was related to the inhibitory effect on ERCC1 expression being mediated by the FGFR2/ERK1/2 signaling pathway.

X-ray repair cross-complementing group 1 polymorphisms and hepatocellular carcinoma:A meta-analysis

AIM： To perform a systematic meta-analysis to in- vestigate the association between X-ray repair crosscomplementing group 1 （XRCC1） polymorphisms and hepatocellular carcinoma （HCC） risk. METHODS： Relevant studies extracted from PubMed, Embase, Wanfang, VIP and the Chinese National Knowledge Infrastructure databases up to March 2012 were included in the study. Stata software, version 11.0, was used for the statistical analysis. The odds ratios （ORs） and 95% confidence interval （CI） of the XRCC1 polymorphisms in HCC patients were analyzed and compared with healthy controls. The meta-analysis was performed using fixed-effect or random-effect methods, depending on the absence or presence of significant heterogeneity. RESULTS： Eleven studies with 2075 HCC cases and 2604 controls met our eligibility criteria （four studies, 888 cases and 938 controls for Arg194Trp, four studies, 858 cases and 880 controls for Arg280His, and nine studies, 1845 cases and 2401 controls for Arg399Gln）. The meta-analysis revealed no associations between the Arg194Trp and Arg399GIn polymorphisms of the XRCC1 gene and HCC risk under all contrast models （codominant, dominant and recessive models） in the overall analysis and sensitivity analysis （the studies with controls not in the Hardy-Weinberg equilibrium were excluded）. For XRCC1 Arg280His polymorphism, the overall analysis revealed the significant associa- tion between the His/His genotype and the increased risk of HCC （His/His vs Arg/Arg model, OR： 1.96, 95% CI： 1.03-3.75, P = 0.04）. However, sensitivity analysis showed an altered pattern of result and non-significant association （OR： 2.06, 95% CI： 0.67-6.25, P = 0.20）. The heterogeneity hypothesis test did not reveal any heterogeneity, and Begg＇s and Egger＇s tests did not find any obvious publication bias. CONCLUSION： The XRCC1 Arg194Trp and Arg399GIn polymorphisms are not associated with HCC risk. More rigorous association studies are needed to verify the involvement ofXRCC1 Arg280His polymorphism in HCC susceptibility.

Tea polyphenols increase X-ray repair cross-complementing protein 1 and apurinic/apyrimidinic endonuclease/redox factor-1 expression in the hippocampus of rats during cerebral ischemia/reperfusion injury

Recent studies have shown that tea polyphenols can cross the blood-brain barrier, inhibit apoptosis and play a neuroprotective role against cerebral ischemia. Furthermore, tea polyphenols can decrease DNA damage caused by free radicals. We hypothesized that tea polyphenols repair DNA damage and inhibit neuronal apoptosis during global cerebral ischemia/reperfusion. To test this hypothesis, we employed a rat model of global cerebral ischemia/reperfusion. We demonstrated that intraperitoneal injection of tea polyphenols immediately after reperfusion significantly reduced apoptosis in the hippocampal CA1 region; this effect started 6 hours following reperfusion. Immunohistochemical staining showed that tea polyphenols could reverse the ischemia/reperfusion-induced reduction in the expression of DNA repair proteins, X-ray repair cross-complementing protein 1 and apudnic/apyrimidinic endonuclease/redox factor-1 starting at 2 hours. Both effects lasted at least 72 hours. These experimental findings suggest that tea polyphenols promote DNA damage repair and protect against apoptosis in the brain.

ERCC1、K-ras、TP-73在替雷利珠单抗联合TP化疗方案治疗非小细胞肺癌中的评估价值

目的研究探讨核苷酸切除修复交叉互补基因1(ERCC1)、Kirsten-Rous肉瘤病毒蛋白(K-ras)、肿瘤蛋白P73(TP73)在替雷利珠单抗结合紫杉醇+顺铂(TP)化疗方案治疗NSCLC中的评估价值。方法选取2020年1月至2021年12月本院收治的126例NSCLC肺癌患者为研究对象,按随机抽签法分为对照组、观察组,各63例。对照组以TP化疗方案治疗,观察组增加替雷利珠单抗治疗。评估组间临床疗效、肿瘤标记蛋白、免疫指标、生存周期、不良反应。结果观察组患者的客观缓解率为69.84%(44/63)高于对照组患者为52.38%(33/63),观察组疾病控制率为82.54%(52/63),高于对照组患者为66.67%(42/63)(P<0.05)。化疗1周期、化疗3周期、化疗6周期时,观察组ERCC1、K-ras、TP-73水平均低于对照组(P<0.05)。治疗后观察组免疫功能补体C3、补体C4、CD40细胞低于对照组,NK细胞高于对照组(P<0.05)。观察组患者的TTP、PFS、总生存期均高于对照组(P<0.05)。观察组不良反应发生率为19.05%(12/63),对照组为12.70%(8/63),组间比较差异无统计学意义(P>0.05)。结论替雷利珠单抗联合TP化疗方案治疗肺癌有良好的治疗效果,能够改善患者免疫功能,延长患者生存周期,治疗安全性较好,且ERCC1、K-ras、TP-73水平变化可反映替雷利珠单抗联合TP化疗方案在肺癌治疗中的效果,在综合疗效评估中有较高的应用价值。

Impact of SNP-SNP interactions of DNA repair gene ERCC5 and metabolic gene GSTP1 on gastric cancer/atrophic gastritis risk in a Chinese population

AIM To investigate the interactions of the DNA repair gene excision repair cross complementing group 5(ERCC5) and the metabolic gene glutathione S-transferase pi 1(GSTP1) and their effects on atrophic gastritis(AG) and gastric cancer(GC) risk.METHODS Seven ERCC5 single nucleotide polymorphisms(SNPs)(rs1047768, rs2094258, rs2228959, rs4150291, rs4150383, rs751402, and rs873601) and GSTP1 SNP rs1695 were detected using the Sequenom MassA RRAY platform in 450 GC patients, 634 AG cases, and 621 healthy control subjects in a Chinese population.RESULTS Two pairwise combinations(ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) influenced AG risk(P_(interaction) = 0.008 and 0.043, respectively), and the ERCC5 rs2094258-GSTP1 rs1695 SNP pair demonstrated an antagonistic effect, while ERCC5 rs873601-GSTP1 rs1695 showed a synergistic effect on AG risk OR = 0.51 and 1.79, respectively). No pairwise combinations were observed in relation to GC risk. There were no cumulative effects among the pairwise interactions(ERCC5 rs2094258 and rs873601 with GSTP1 rs1695) on AG susceptibility(P_(trend) > 0.05). When the modification effect of Helicobacter pylori(H. pylori) infection was evaluated, the cumulative effect of one of the aforementioned pairwise interactions(ERCC5 rs873601-GSTP1 rs1695) was associated with an increased AG risk in the case of negative H. pylori status(P_(trend)= 0.043).CONCLUSION There is a multifarious interaction between the DNA repair gene ERCC5 SNPs(rs2094258 and rs873601) and the metabolic gene GSTP1 rs1695, which may form the basis for various inter-individual susceptibilities to AG.

DNA repair gene XRCC1 polymorphisms and susceptibility to childhood acute lymphoblastic leukemia: a meta-analysis

Objective： To estimate the relationship between genetic polymorphisms of X-ray repair cross- complementing group 1 （XRCC1） and the susceptibility to childhood acute lymphoblastic leukemia （ALL）. Methods： Relevant case-control studies were enrolled in the meta-analysis. We applied Rev Man 4.2 software to pool raw data and test studies＇ heterogeneity and to calculate the incorporated odds ratio （OR） and 95% confidence interval （95% CI）. Results： Our data showed that the OR for the Gln allele of the Arg399Gln polymorphism, compared with the Arg allele, was 1.35 （95% CI, 1.16-1.57; P〈0.0001） for childhood ALL patients. Similarly, the homozygous genotype Gln/Gln and heterozygous genotype Arg/Gln both significantly increased the risk of childhood ALL compared with the wild genotype Arg/Arg （OR =1.58; 95% CI, 1.13-2.21; P=0.008; OR =1.51; 95% CI, 1.21-1.87; P=0.0002）. The dominant model of Arg399Gln was associated with childhood ALL risk （OR =1.54; 95% CI, 1.25-1.89; P〈0.0001）. The ethnic subgroup analysis demonstrated that the Gln allele in all five ethnic groups was prone to be a risk factor for childhood ALL just with different degrees of correlation while Arg194Trp SNP showed a protective or risk factor or irrelevant thing in different races. Conclusions： XRCC1 399 polymorphism may increase the risk of childhood ALL. Different ethnic groups with some gene polymorphism have different disease risks.

Neuronal effects of SP600125 pretreatment in a rat model of cerebral ischemia/reperfusion injury Inhibited down-regulation of DNA repair protein

BACKGROUND： Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases （JNKs） signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE： To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi＇an Jiaotong University from June 2007 to September 2008. MATERIALS： SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK （Thr183/Tyr185） polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 （XRCC1） and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS： A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group （I/R group） were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group （pre-SP group） was given 10 μL SP600125 （3 μg/μL）. Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES： Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS： Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased （P 〈 0.01）. Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased （P 〈 0.01）. Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased （P 〈 0.05） following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group （P 〈 0.05）. Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region （r = -0.983, -0.953, P 〈 0.01）. CONCLUSION： SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.

吸烟对非小细胞肺癌患者ERCC1和RRM1表达的影响及与预后的相关性

目的探讨吸烟对非小细胞肺癌(NSCLC)患者切除修复交叉互补基因1(ERCC1)和核糖核苷酸还原酶M1(RRM1)表达的影响及其与预后的关系。方法收集2015年8月至2018年8月河南科技大学第一附属医院收治的131例ⅢB期、Ⅳ期的NSCLC患者。依据有无吸烟史将患者分为两组,其中非吸烟组64例,吸烟组67例,检测各组ERCC1和RRM1的表达水平,分析其与患者临床资料的相关性以及对患者预后的影响。结果吸烟组ERCC1高表达患者占比多于非吸烟组(P<0.05);两组ERCC1和RRM1的表达水平与患者性别、年龄、肿瘤大小、病理类型无关(P>0.05);吸烟指数≥400的患者ERCC1表达较高(P=0.018);两组ERCC1和RRM1低表达的患者化疗有效率均高于高表达患者(χ^(2)=6.194,P=0.013;χ^(2)=5.012,P=0.025);与吸烟组比较,非吸烟组化疗有效率高(P=0.045),1 a复发率低(P=0.001),无进展生存期(P=0.008)和总生存期长(P=0.005)。结论吸烟影响ERCC1的表达,且吸烟指数越高的患者ERCC1表达越高;而RRM1的表达与吸烟无关。吸烟患者化疗有效率、1 a复发率低于非吸烟患者,无进展生存期及生存期均短于非吸烟患者。

ERCC1 mRNA和X线修复交叉互补组1基因多态性联合检测在局部晚期鼻咽癌患者放化疗中的应用价值

目的 探讨核苷酸切除修复交叉互补组1(ERCC1)m RNA和X线修复交叉互补组1(XRCC1)基因多态性联合检测在局部晚期鼻咽癌患者放化疗中的应用价值。方法 选取2020年1月至2021年1月在江西省上饶市人民医院接受放化疗的41例局部晚期鼻咽癌患者,采用定量反转录聚合酶链反应检测外周血中ERCC1 mRNA的表达水平,采用限制性片段长度多态性聚合酶链反应检测XRCC1基因型(Arg194Trp、Arg280His、Arg399Gln),探讨ERCC1 mRNA和XRCC1多态性与局部晚期鼻咽癌患者放化疗效果、肿瘤复发及药物不良反应(ADR)的关系,并采用logistic回归分析局部晚期鼻咽癌患者ADR的影响因素。结果 完全缓解和部分缓解患者的ERCC1 mRNA及XRCC1多态性与疾病稳定和疾病进展患者比较差异无统计学意义(P>0.05)。肿瘤复发患者的ERCC1 mRNA及XRCC1多态性与非复发患者比较差异无统计学意义(P>0.05)。ADR患者XRCC1 Arg194Trp位点携带AG基因型、ERCC1 mRNA高表达的频率均高于非ADR患者,差异有统计学意义(P<0.05)。多因素logistic回归分析显示,XRCC1 Arg194Trp AG基因型(OR=1.876)、ERCC1mRNA高表达(OR=1.109)是局部晚期鼻咽癌患者放化疗期间发生ADR的影响因素(P<0.05)。结论 与单一检测相比,ERCC1 mRNA和XRCC1多态性联合检测预测局部晚期鼻咽癌患者放化疗期间ADR的价值更高,值得临床应用。

上皮性卵巢癌中ERCC1及转录因子Nanog蛋白的表达水平及意义

目的探讨上皮性卵巢癌中核昔酸切除修复交叉互补组1(ERCC1)及转录因子Nanog蛋白的表达水平及意义。方法收集2019年1月至2022年12月在连云港市肿瘤医院妇科行卵巢手术切除的组织标本,其中上皮性卵巢癌组织标本101例(上皮性卵巢癌组),良性卵巢肿瘤组织标本80例(对照组),采用免疫组化检测ERCC1及Nanog蛋白表达水平,并分析与临床病理指标的关系。分别用0mg/L、1mg/L、2mg/L、4mg/L不同浓度的顺铂处理人卵巢癌OVCAR-3细胞24h,以Western blot检测细胞中ERCC1、Nanog蛋白的相对表达量,比较两组间ERCC1及Nanog蛋白的表达水平。结果上皮性卵巢癌组ERCC1、Nanog蛋白的阳性率均明显高于对照组,差异均有统计学意义(χ^(2)值分别为49.960、39.941,P<0.05)。Spearman相关性分析显示,上皮性卵巢癌组中ERCC1与Nanog蛋白表达水平呈正相关(r=0.463,P<0.01);对照组中ERCC1与Nanog蛋白表达水平无相关性(r=0.125,P>0.05)。在上皮性卵巢癌临床病理指标中,FIGO分期为Ⅲ+Ⅳ期的ERCC1、Nanog蛋白的阳性率均明显高于Ⅰ+Ⅱ期(χ^(2)值分别为9.578、9.756),淋巴结转移阳性的ERCC1、Nanog蛋白阳性率均明显高于淋巴结转移阴性(χ^(2)值分别为3.018、2.389),经比较差异均有统计学意义(P<0.05)。1mg/L、2mg/L、4mg/L浓度顺铂处理的ERCC1和Nanog蛋白相对表达量均明显高于0mg/L浓度顺铂处理的相对表达量,经比较差异均有统计学意义(F值分别为8.564、6.571,P<0.05);在ERCC1、Nanog蛋白相对表达量中,顺铂处理浓度1mg/L与0mg/L相比(t值分别为17.236、5.381)、顺铂处理浓度2mg/L与0mg/L相比(t值分别为5.621、6.380)、顺铂处理浓度4mg/L与0mg/L相比(t值分别为12.813、6.810),差异均有统计学意义(P<0.05);且随顺铂浓度的增加,ERCC1、Nanog蛋白相对表达量逐渐升高。结论ERCC1及Nanog蛋白在上皮性卵巢癌中呈现出高表达,可能与该病的发病机理和病情发展具有相关性。顺铂可诱导卵巢癌细胞ERCC1及Nanog蛋白高表达,可能为化疗耐药的潜在机制。

ERCC1蛋白表达与局部晚期鼻咽癌同步放化疗疗效的关系

目的：探讨切除修复交叉互补基因1（ ERCC1）在鼻咽癌组织中的表达，并分析其表达与局部晚期鼻咽癌同步放化疗疗效的关系。方法收集2010年1月至2010年12月经鼻咽部肿物活检确诊均为非分化型非角化性鼻咽癌患者76例，给予顺铂单药同步放化疗。化疗方案具体为顺铂80mg／m2，静脉滴注，于放疗第1、22、43天进行；放疗采用常规分割照射，5次／周，鼻咽平均剂量74Gy（70～78Gy），同步放化疗结束后评价其近期疗效并随访远期生存情况。应用免疫组化法检测鼻咽癌组织中ERCC1蛋白表达，分析其表达与同步放化疗近期疗效及远期生存率的关系。结果76例鼻咽癌组织中ERCC1蛋白的阳性表达率为42.1％（32／76）。 ERCC1蛋白表达与鼻咽癌的T分期、临床分期有关（P＜0.05），而与性别、年龄及N分期无关（P＞0.05）。 ERCC1蛋白阳性表达者的有效率（RR）为75.0％（24／32），ERCC1阴性表达者的RR为97.7％（43／44），差异有统计学意义（ P＝0.008）。获得随访的72例患者的1年、2年、3年生存率分别为91.0％、83.3％、79.0％。 ERCC1阴性表达者的1年、2年、3年生存率分别为92.4％、87.8％、80.5％， ERCC1阳性表达者的1年、2年、3年生存率分别为87.9％、77.4％、77.4％，两者的中位生存期（ OS）差异无统计学意义（ P＞0.05）。ERCC1阳性表达者中不同分级的中位OS差异有统计学意义（ P＜0.05）。结论 ERCC1蛋白的表达可能是预测局部晚期鼻咽癌同步放化疗近期疗效及预后的指标。

晚期非小细胞肺癌组织中ERCC-1、Metallothionein、p53表达与铂类耐药性及预后的相关性分析

背景与目的晚期非小细胞肺癌含顺铂方案化疗敏感性分子预测指标尚处于探索阶段。本研究分析晚期非小细胞肺癌石蜡包埋组织中错配切除修复蛋白(excisionrepaircrosscomplement-1,ERCC-1)、金属硫蛋白(metallothionein,MT)、p53蛋白与顺铂化疗敏感性的关系,并观察这些指标与病人生存的关系。方法收集1994年1月-2001年12月在本院经病理组织学诊断的用含铂方案(Gemzar+DDP或NVB+DDP)化疗的初治晚期非小细胞肺癌患者的病理标本,采用免疫组化方法检测ERCC-1、MT、p53的表达,并将病人的疗效和生存资料与上述指标的表达进行比较。样本率的比较用χ2检验,用Kaplan-meier法和Cox回归进行生存分析。结果本组51例标本中,ERCC-1阳性率为42.8%,MT阳性率为57.5%,p53阳性率为37.8%。化疗有效率在ERCC-1、MT、p53阴性组和阳性组分别为33.3%、35.3%、21.4%和16.7%、27.3%、35.3%(即分别为1.99倍,1.29倍,0.61倍),但均未达统计学差异(P>0.05),ERCC-1,MT均阴性组有效率为37.5%,均阳性组有效率为14.3%,前者为后者的2.6倍,但未达统计学差异(P>0.05)。平均生存期ERCC-1、MT、p53蛋白阴性组和阳性组分别为621.03天/523.14天,556天/479天,599.64天/416.60天。Kaplan-meier分析显示三者过度表达均提示预后不良,但Cox回归分析显示只?

ERCC1在鼻咽癌组织中的表达及其与顺铂化疗敏感性的关系

目的:探讨核苷酸切除修复交叉互补基因1(excision repair cross-complementing 1,ERCC1)在鼻咽癌(nasopharyn-geal carcinoma,NPC)组织中的表达及其与顺铂化疗敏感性的关系。方法:选取广西南溪山医院2006年6月至2008年6月确诊的82例中晚期NPC患者,接受顺铂+5-FU的基础化疗加放疗,应用免疫组化法检测NPC癌组织中ERCC1蛋白的表达及其中的34例患者癌旁上皮组织(对照组)中ERCC1蛋白的表达。结果:NPC癌旁上皮组织中ERCC1的阳性率为88.2%,显著高于NPC癌组织中ERCC1的阳性率63.4%(P<0.05)。ERCC1表达与NPC患者年龄有关(P<0.05),而与性别、T分期、N分期、M分期无关(P>0.05)。ERCC1蛋白表达阳性的NPC患者化疗有效率为36.5%,ERCC1阴性患者化疗有效率为63.3%,两者差异有统计学意义(P<0.05)。结论:ERCC1在中晚期NPC癌组织中低表达,ERCC1表达与顺铂+5-FU方案的疗效呈负相关,检测ERCC1表达有助于预测NPC患者对顺铂化疗的敏感性。

18F-fluorodeoxyglucose Uptake with Expression of Excision Repair Cross-complementary Group I and Ribonucleotide Reductase Subunit M1 in Non-small Cell Lung Cancer

Fluorodeoxyglucose positron emission tomography/conlputed tomography （FDG PET/CT） is widely applied in non-small cell lung cancer （NSCLC）. The standardized uptake value （SUV）, a semi-quantitative index, plays an essential role in NSCLC tbr diagnosis, staging, and efficacy evaklation. It has been px3posed that the SUV of tumors may correlate with the presence or absence of chemotherapy resistance-associated biomarkers based on studies that have displayed a close correlation between SUV and the expression levels of excision repair cross-complementary Group 1 （ERCC 1 ）1~1 and Tp53-induced glycolysis and apoptosis regulator.121 FDG avidity of NSCLC and ERCC 1 and ribonucleotide reductase subunit M 1 （RRM 1 ） levels have not been as extensively investigated. Based on these findings, we looked tbr correlations among metabolic parameters （SUVm,,. metabolic tumor volume [MTV], and total lesion glycolysis [TLG]） and ERCC1 and RRM1 expression in patients with NSCLC, to investigate whether FDG uptake reflects the presence or absence ofchemoresistance proteins （ERCC1 and RRM 1 ） within tumor cells.

食管癌组织中ERCC1和GSTP1表达量与铂类化疗药物敏感性及凋亡、增殖基因表达量的相关性

目的:研究食管癌组织中ERCC1和GSTP1表达量与铂类化疗药物敏感性及凋亡、增殖基因表达量的相关性。方法:选择在我院接受PF方案化疗的晚期食管癌患者,化疗前收集食管癌组织并根据化疗后的效果分为化疗敏感组和化疗耐药组,检测食管癌组织中ERCC1、GSTP1以及凋亡基因、增殖基因的表达量。结果:化疗敏感组食管癌组织中ERCC1、GSTP1的蛋白含量以及蛋白阳性表达率均显著低于化疗耐药组,MBP1、DEC1、PTEN的蛋白含量显著高于化疗耐药组,PLCE1、CyclinD1、PAR2的蛋白含量显著低于化疗耐药组;ERCC1、GSTP1阳性表达食管癌组织中MBP1、DEC1、PTEN的蛋白含量显著低于ERCC1、GSTP1阴性表达食管癌组织,PLCE1、CyclinD1、PAR2的蛋白含量显著高于ERCC1、GSTP1阴性表达食管癌组织。结论:食管癌组织中高表达的ERCC1和GSTP1能够降低癌细胞对铂类化疗药物的敏感性,在铂类药物化疗过程中抑制细胞凋亡、促进细胞增殖。

大肠癌中医证型与ERCC1基因多态性的相关研究

目的探讨大肠癌中医证型与核苷酸切除修复交叉互补基因1(excision repair cross-complementing 1,ERCC1)C8092A和C19007T两个位点基因多态性的关系。方法 99例大肠癌患者经中医辨证分为湿热蕴结、气滞血瘀、脾肾阳虚及肝肾阴虚4个证型。应用PCR扩增和直接测序法检测患者外周静脉血ERCC1C8092A和C19007T两个位点基因型及等位基因在大肠癌各证型的分布情况,并进行统计学分析。结果 ERCC1C8092A基因型及等位基因频率在各证型间的分布比较,差异均无统计学意义(P>0.05)。ERCC1C19007T基因型及等位基因频率在各证型间的分布频率比较,差异有统计学意义(P<0.05),其中湿热蕴结型与气滞血瘀型、脾肾阳虚型与肝肾阴虚型差异无统计学意义(P>0.05),湿热蕴结型与脾肾阳虚型、肝肾阴虚型差异有统计学意义(P<0.05),气滞血瘀型与脾肾阳虚型、肝肾阴虚型差异有统计学意义(P<0.05)。结论 ERCC1C19007T基因多态性可能与大肠癌中医证型有关,需要进一步研究。

ERCC1、RRM1表达对肺癌患者术后吉西他滨联合顺铂化疗生存趋势的影响

背景与目的肺癌化疗疗效与肿瘤的基因表达有关,本研究拟探讨ERCC1、RRM1表达与非小细胞肺癌术后吉西他滨联合顺铂(GP)辅助化疗预后的关系。方法随访57例临床Ⅱ-Ⅳ期接受手术治疗的非小细胞肺癌患者,其中术后接受2周期以上化疗者39例(化疗组),未化疗者18例(未化疗组)。采用免疫组化法检测ERCC1、RRM1表达,Cox回归分析筛选影响预后的独立危险因子,Kaplan-Meier生存曲线分析比较各组患者的中位生存时间。结果Cox回归分析显示手术彻底程度、术后辅助化疗与否、ERCC1表达水平为影响术后生存时间的独立危险因子。ERCC1低表达组中化疗组和未化疗组中位生存期分别为23个月和21个月(P=0.088),ERCC1高表达组中化疗组和未化疗组中位生存期分别为42个月和12个月(P=0.018)。RRM1低表达组中化疗组和未化疗组中位生存期分别为42个月和22个月(P=0.010),RRM1高表达组中化疗组和未化疗组中位生存期分别为28个月和21个月(P=0.092)。结论ERCC1高表达、RRM1低表达的非小细胞肺癌患者更能从术后吉西他滨联合顺铂的化疗中受益。

BER通路中XRCC1多位点单核苷酸多态性与新疆不同民族喉癌易感性相关性研究

背景与目的:影响肿瘤遗传易感性的修复基因主要存在修复通路碱基切除修复(base excision repair,BER)途径,而X射线交错互补修复基因1(X-ray repair cross complementing group 1,XRCC1)是BER通路中的核心基因。近几年,国内外开展了许多有关基因多态性和喉癌易感性的研究。探讨BER通路DNA修复基因XRCC1多位点单核甘酸多态性与新疆不同民族喉癌易感性关系。方法:采用患者组与对照组的研究方法,选择58例喉癌(经病理证实为鳞状细胞癌)患者和120名体检正常的健康人对照,应用Multiplex SNa Pshot技术检测DNA碱基切除修复基因XRCC1的Gln632Gln(rs3547)、Arg399Gln(rs25487)、Arg280His(rs25489)、Arg194Trp(rs1799782)位点单核苷酸多态在患者组和正常对照组中的分布情况。结果:喉癌患者组中XRCC1Arg280His(rs25489)C/T(杂合型)及T/T(突变型)基因型的比例与对照组比较差异无统计学意义(P>0.05)。喉癌患者组中XRCC1的其余3个位点Gln632Gln(rs3547)C/T(杂合型)及T/T(突变型)基因型、Arg399Gln(rs25487)C/T(杂合型)及T/T(突变型)基因型、Arg194Trp(rs1799782)G/A(杂合型)及A/A(突变型)基因型的比例明显高于对照组(P<0.01)。其中汉、维、哈3个民族患者组Gln632Gln(rs3547)C/T(杂合型)及T/T(突变型)基因型、Arg399Gln(rs25487)C/T(杂合型)及T/T(突变型)基因型、Arg194Trp(rs1799782)G/A(杂合型)及A/A(突变型)基因型比例显著高于对照组(P<0.05),携带(rs3547)C/T及T/T基因型、(rs25487)C/T及T/T基因型、(rs1799782)G/A及A/A基因型个体较携带XRCC1(rs3547)C/C基因型、(rs25487)C/C基因型、(rs1799782)G/G基因型的个体患喉鳞状细胞癌的风险升高了分别为0.96倍、1.74倍、1.39倍;1.47倍、1.32倍、0.77倍,1.49倍、1.51倍、1.56倍。结论:汉、维、哈3个民族的XRCC1 Gln632Gln、Arg399Gln、Arg280His、Arg194Trp位点的单核苷酸多态性可能与喉癌遗传性有关联且有差异,XRCC1基因中的Gln632Gln、Arg399Gln、Arg194Trp位点的突变将导致喉癌的发病风险升高。而XRCC1基因中的Arg280His位点突变与喉癌发病的差异无统计学意义,可能该位点的突变与喉癌发病无关。

XRCC1基因多态性与宫颈鳞癌放疗敏感性的关系

目的探讨XRCC1基因Arg194Trp、Arg399Gln单核苷酸多态性(SNP)与外生型宫颈鳞状细胞癌放疗敏感性的关系。方法选择经组织病理学确诊的外生型宫颈鳞状细胞癌患者73例。其中临床分期Ⅰ期4例,Ⅱ期36例,Ⅲ期30例,Ⅳ期3例。肿瘤直径≤4 cm 30例,肿瘤直径>4 cm 43例;A点剂量≤80 Gy者36例,A点剂量>80 Gy者37例。近期疗效为完全缓解者(CR组)47例,部分缓解者(PR组)26例。采用错配扩增聚合酶链式反应检测患者血液标本的XRCC1 Arg194Trp、Arg399Gln SNP的基因型频率分布,分析其与宫颈癌放疗敏感性的关系。结果 XRCC1基因Arg194Trp分型中,携带Arg/Arg、Arg/Trp、TrP/Trp分别有31例(42.5%)、37例(50.7%)、5例(6.8%);Arg399Gln分型中,携带Arg/Arg、Arg/Gln、Gln/Gln分别有26例(35.6%)、39例(53.4%)、8例(11.0%)。CR组与PR组Arg194Trp、Arg399Gln基因型分布差异均无统计学意义。影响放疗敏感性的多因素Logistic回归分析结果显示,临床分期晚为PR的危险因素。结论 XRCC1基因Arg194TrpSNP、Arg399Gln SNP与外生型宫颈鳞状细胞癌放疗敏感性无相关性。临床分期越晚放疗敏感性越差。

乳腺癌新辅助化疗对ERCC1基因表达的影响

目的探讨核苷酸切除修复基因家族成员ERCC1基因在乳腺癌中的表达情况和新辅助化疗对它的影响及临床意义。方法RT-PCR检测40例常规手术切除的乳腺癌标本和14例术前曾接受新辅助化疗的乳腺癌标本中ERCC1基因的表达。结果乳腺癌中ERCC1基因阳性表达率为35.0%,其表达水平与患者的年龄、肿瘤大小、淋巴结转移、病理分型、组织学分级、ER、PR和HER-2均无明显相关性(P>0.05)。新辅助化疗组ERCC1基因的表达水平明显高于无化疗组(P<0.05)。结论ERCC1基因的表达不影响乳腺癌的临床病理特征,新辅助化疗可以上调ERCC1基因的表达水平,在临床后续化疗中应予重视。