Role of ERCC1 expression in colorectal adenoma-carcinoma sequence and relation to other mismatch repair proteins expression, clinicopathological features and prognosis in mucinous and non-mucinous colorectal carcinoma

Background: There are several DNA repair pathways that protect cellular DNA from injury, such as nucleotide excision repair (NER) and mismatch repair (MMR). The protein product of the excision repair cross-complementation group 1 (ERCC1) gene plays a pivotal role in NER. The exact relationship between MMR proteins and ERCC1 is not well known in colorectal carcinoma (CRC). Aim of the Study: To investigate expression of ERCC1 and MMR proteins in colorectal mucinous carcinoma (MA) and non-mucinous carcinoma (NMA) using tissue microarray technique. Material and Methods: We studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and non-mucinous adenocarcinoma (NMA). Tissue microarrays were constructed using modified mechanical pencil tips technique and immunohistochemistry for ERCC1, MLH1, MSH2, MSH6, and PMS2. Results: NMA showed a significantly more frequent aberrant cytoplasmic expression than MA while MA showed a more frequent intact nuclear expression than NMA. There were no significant differences between the NMA and MA groups in the expression of MMR proteins. In NMA cases, ERCC1 expression was significantly related to MMR status while was not significantly related in MA cases. ERCC1 expression was not significantly related to overall and disease-free survival in both NMA and MA groups. Conclusion: this study is the first to investigate the relation between MMR status and ERCC1 expression in colorectal MA and NMA. ERCC1 expression was significantly related to MMR status only in NMA cases. Hence, the current study emphasizes that further research about the relation between various DNA repair pathways is needed.

Immunohistochemistry Biomarkers Predict Survival in Stage II/III Gastric Cancer Patients: From a Prospective Clinical Trial / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection. MATERIALS AND METHODS: This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomywith orwithout adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values. RESULTS: Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis. CONCLUSION: This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.

Mechanisms of miR-503 inhibiting radio-resistance of esophageal squamous cell carcinoma cells by targeting ERCC1 / 中国肿瘤生物治疗杂志

@# Objective: To investigate the mechanism of miR-503 modulates radio-resistance of esophageal squamous cell carcinoma (ESCC) by targeting excision-repair cross-complementing 1 (ERCC1). Methods: The expression level of miR-503 in radio-resistant ESCC tumor tissues and KYSE140 and KYSE140R cells was detected by qPCR. The miR-503 mimic, miR-503 inhibitor or si-ERCC1 was transfected into KYSE140 and KYSE140R cells.After radiation treatment, the colony formation assay and CCK-8 assay were used to detect the proliferation of KYSE140R cells. Flow cytometry was used to detect apoptosis of KYSE140R cells. WB was used to detect changes in protein expression of ERCC1. Dual luciferase reporter gene assay was used to validate the targeting relationship between miR-503 and ERCC1. Results: The expression level of miR-503 was down-regulated in radio-resistant tissues and ESCC cell lines (all P<0.01). Over-expression of miR-503 significantly inhibited cell proliferation and promoted apoptosis of KYSE140R cells (all P<0.01). Dual-luciferase reporter assay validated that ERCC1 was a target gene of miR-503, and miR-503 negatively regulated the expression of ERCC1. Over-expression of miR-503 significantly down-regulated the expression of ERCC1 in KYSE140 and KYSE140R cells (both P<0.01), inhibited cell proliferation (both P<0.01), but significantly increased apoptosis rate (all P<0.01); knockdown of ERCC1 exhibited a similar effect, while knockdown of both ERCC1 and miR-503 reversed the above effects. Conclusion: Over-expression of miR-503 up-regulated the radio-sensitivity of KYSE140R cells by targeting ERCC1.

Association between nucleotide excision repair cross-complementing gene polymorphism and susceptibility to endemic arsenic poisoning / 中华地方病学杂志

Objective To investigate the relationship between nucleotide excision repair cross-complementing (ERCC) gene polymorphisms [single nucleotide polymorphism (SNP) sites: rs11615, rs13181, rs238406, rs6498486, rs17655] and susceptibility to endemic arsenic poisoning. Methods The study recruited 848 subjects, including 348 cases and 500 controls, from populations exposed to high arsenic levels through drinking water in northwest China, and 3 - 5 ml venous blood was collected. The genotypes were determined using polymerase chain reaction and restriction fragment length polymorphism techniques(PCR-RFLP). Logistic regression analysis was used to assess the association of genotypes with endemic arsenic poisoning. Results The polymorphisms of rs11615 (ERCC1), rs238406 (ERCC2), rs6498486 (ERCC4) and rs17655 (ERCC5) and endemic arsenic poisoning were not related(P > 0.05). Participants who carried the CC genotype or at least one C allele for the ERCC2 rs13181 had an increased risk of endemic arsenic poisoning[OR(95%CI)=1.63(1.13,2.34),1.64(1.14,2.34)]compared with wild type homozygous individuals. Conculsions There is no positive correlation between the polymorphisms of ERCC1 rs11615, ERCC2 rs238406, ERCC4 rs6498486, ERCC5 rs17655 and endemic arsenic poisoning. ERCC2 rs13181 polymorphism increases the risk of endemic arsenic poisoning.

Clinical and molecular genetic study of Cockayne syndrome accompanied with nephrotic syndrome in a family / 中华实用儿科临床杂志

Objective To analyze the clinical and genetics characteristics in twin sisters with Cockayne syn-drome.Methods The identical twin sisters visited the Affiliated Children's Hospital of Capital Institute of Pediatrics in December 2016.The clinical presentations,course of treatment,blood biochemistry,metabolic screening and whole exon sanger sequencing were analyzed.Results These two patients were referred at 4 years and 5 months of age for growth failure and developmental delay.The younger sister manifested short stature(only 97 cm),low weight(14.0 kg)and little head circumference(43 cm),and the elder sister manifested short stature(only 98 cm),low weight(15.5 kg) and little head circumference(43 cm).They were born with out adverse event,and then they kept the head up at 8 months of age.They could sit at 10 months of age,but they had not acquired independent walking ability up till now. They spoke their first words at 2 year of age,and made little progress after that.They had a variety of abnormal clinical features including cognitive deficits,microcephaly,thin pointy nose,sunken eyes,small chin,photosensitive rash,hearing impairment,volitional tremor and hypermyotonia.They had been diagnosed as nephrotic syndrome at 4.5 years old,with little response to prednisone.The renal biopsy revealed minimal change nephropathy.Cerebrum and cerebellum atrophy was detected by magnetic resonance image scanning. Two heterozygous ERCC8 mutations in both patients,c.394_398delTTACA and large fragment deletion,were identified in the patient.The c.394_398delTTACA mutation originated from his father. The exon 4 deletion from his mother caused the defection of the protein. Conclusions Cockayne syndrome is a rare autosomal recessive disease. It is not only characterized by developmental delay,microcephaly, sunken eyes,photosensitive rash and auditory abnormalities,but also can be involved in nephrotic syndrome.Cockayne syndrome can be caused by compound heterozygous mutation,including c.394_398delTTACA and a large fragment deletion of exon 4 in ERCC8.

Clinical characteristics, treatment and follow-up of Cockayne syndrome with renal involvement / 临床儿科杂志

Objective To explore the clinical features, treatment and follow-up of Cockayne syndrome with renal involvement. Method The clinical data of one child with Cockayne syndrome confirmed by gene detection with renal injury were reviewed, and the clinical features of renal involvement in Cockayne syndrome were summarized. Results A male child aged 3 years and 8 months had clinical manifestations of mental retardation, growth retardation, special face and photosensitive dermatitis, and renal involvement was manifested by nephrotic syndrome. Cranial CT showed symmetrically calcification in bilateral basal ganglia. The targeted next generation sequencing results showed homozygous mutations of c.394_398del and p.Leu132Asnfs in ERCC8 gene (NM_000082) of the child, and the same heterozygous mutation was found in both his parents (non-consanguineous marriage). After the diagnosis of nephrotic syndrome, full dose prednisone was given for experimental treatment. The urine protein decreased but did not disappear, which was considered hormone resistance. After 4 months of combined treatment with cyclosporin, the urine protein turned negative. During 20 months of follow-up, urine protein remained negative and renal function remained stable. The renal involvement in Cockayne syndrome was seldomly reported, and its clinical manifestations are heterogeneous. Condusion Renal involvement in Cockayne syndrome may be manifested with nephrotic syndrome which should be noticed.

Radiotherapy modulates expression of EGFR, ERCC1 and p53 in cervical cancer

Cervical cancer is a public health problem and the molecular mechanisms underlying radioresistance are still poorly understood. Here, we evaluated the modulation of key molecules involved in cell proliferation, cell cycle and DNA repair in cervical cancer cell lines (CASKI and C33A) and in malignant tissues biopsied from 10 patients before and after radiotherapy. The expression patterns of epidermal growth factor receptor (EGFR), excision repair cross-complementation group 1 (ERCC1) and p53 were evaluated in cancer cell lines by quantitative PCR and western blotting, and in human malignant tissues by immunohistochemistry. The mutation status of TP53 gene was evaluated by direct sequencing. Among cell lines, absent or weak modulations of EGFR, ERCC1 and p53 were observed after exposure to 1.8 Gy. Conversely, increased expressions of p53 (5/10 patients; P=0.0239), ERCC1 (5/10 patients; P=0.0294) and EGFR (4/10 patients; P=0.1773) were observed in malignant tissues after radiotherapy with the same radiation dose. TP53 mutations were found only in one patient. Here we show that a single dose of radiotherapy induced EGFR, ERCC1 and p53 expression in malignant tissues from cervical cancer patients but not in cancer cell lines, highlighting the gap between in vitro and in vivo experimental models. Studies on larger patient cohorts are needed to allow an interpretation that an upregulation of p53, EGFR and ERCC1 may be part of a radioresistance mechanism.

Relationship between the Asp1104His polymorphism of the nucleotide excision repair gene ERCC5 and treatment sensitivity to oxaliplatin in patients with advanced colorectal cancer in China

OBJECTIVES: To study the relationship between the Asp1104His polymorphism of the nucleotide excision repair gene ERCC5 and treatment sensitivity to oxaliplatin in patients with advanced colorectal cancer (CRC) in China. METHODS: A group of 226 patients in the Department of Gastrointestinal Oncology at Zhejiang Xiaoshan Hospital from July 2011∼December 2016 and a control group of 226 normal healthy individuals were involved in this study. All patients were first diagnosed with advanced CRC and were treated with oxaliplatin-based chemotherapy. The genotype of ERCC5 at the site of amino acid 1104 was determined by a TaqMan probe-based real-time PCR approach. RESULTS: There were no differences in age or gender between the groups, but the percentages of smokers and individuals with a family history of cancer were significantly higher in the patient group than in the control group. Analysis of the G/C polymorphism frequency among the patients and the healthy controls showed that the frequencies of the CC genotype and the CC+GC genotype were significantly related to CRC, but no significant difference in these frequencies was found between genders. The analysis of the relationship between the 5-year survival rate and different genotypes showed that in the total patient group, regardless of gender, the 5-year survival rate was significantly associated with the Asp1104His polymorphism of ERCC5. CONCLUSIONS: The Asp1104His polymorphism of ERCC5 was associated with the risk and 5-year survival rate of CRC as well as treatment sensitivity to oxaliplatin.

Patients with advanced gastric cancer in Qinghai Tibetan TSER, ERCC1, polymorphism and mRNA significance / 实用医学杂志

Objective To discuss progress in Qinghai Tibetan Thymidylate synthase enhancer in patients with gastric cancer (TSER),ERCC1 polymorphism of genes,gene expression and mRNA studies.Methods 210 cases of advanced gastric cancer were enrolled as required to complete the treatment and follow-up.TSER,ERCC 1 gene polymorphism were tested using PCR-RFLP method.Analysis of gastric cancer is based on the results of gene polymorphism and clinical pathological factors in relations.The expression of ERCC1 mRNA was detected by RTPCR,and tracking access after treatment.Analyzing the relationship among ERCC1 mRNA expression,clinical treatment of overall survival,total response rates and gene polymorphism.Results In patients with advanced gastric C/C in Qinghai ERCC1 gene frequency was 54.2％,C/T frequency was 42.7％,T/T ERCC1 gene frequency was 5.6％.ERCC1 mRNA expression and clinical effect in the treatment of pathological factors were not related,ERCC1 mRNA and gene ERCC1 polymorphism had no relevance.Conclusions Progress in Qinghai Tibetan TSER gene is highly expressed type 3R/3R in patients with gastric cancer.ERCC 1 gene polymorphisms with type C/ C is overexpressed.ERCC1,TSER gene polymorphism and clinicopathologic parameters in advanced gastric is not related.Extension of Tibetan ERCC1 mRNA in gastric cancer patients expression has no association with ERCC1 gene polymorphism.

Clinical and genetic study of a family with cerebro-oculo-facio-skeletal syndrome / 中华实用儿科临床杂志

Objective To analyze the clinical features and pathogenic gene mutation in a Chinese family with cerebro-oculo-facio-skeletal(COFS)syndrome,in order to summarize the relationship between phenotype and genotype.Methods The clinical data of the proband and his family members were collected.Genomic DNA from the proband and his parents were extracted by using standard procedures from the peripheral blood leukocytes.Next-generation sequencing was used to detect gene mutation in the patient with COFS syndrome.Sanger sequencing was applied to confirm the results.Results The proband,male,1 year and 3 months old,presented with microcephaly nystagmus,large ears,prominent nose,high arched palate,overhanging upper lip,micrognathia,widely set nipples,flexion contractures(especially involving the elbows and knees),failure to thrive,developmental retardation and feeding difficulty.His parents were normal phenotype.Two different heterozygous mutations c.1843G>T(P.G615W)and c.1996 C> T(P.R666W)were identified in the ERCC2 gene.The proband's father had the heterozygous mutation c.1843G>T(P.G615W)and his mother had the heterozygous mutation c.1996 C> T(P.R666W).Meanwhile,this heterozygous mutation c.1996 C> T(P.R666W)had been reported as a pathogenic gene mutation.Conclusions COFS syndrome is characterized by microcephaly,prominent nose,arthrogryposis and severe developmental delay.This is the first report on COFS syndrome patient in the mainland of China.The pathogenic gene mutations and gene status were identified through genetic studies.The result has laid the foundation for accurate genetic counseling and further prenatal diagnosis.

Clinical expression of P53,Livin and PARP in the epithelial ovarian cancer and its impact in the chemotherapy resistance and clinical prognosis / 中国生化药物杂志

Objective To explore the clinical expression of P53, Livin and PARP in the epithelial ovarian cancer and its correlation with the chemotherapy resistance and clinical prognosis.Methods 74 specimen of epithelial ovarian cancer confirmed from January 2009 to June 2011 in our gynecology department were selected.During the follow-up visit, the subjects were divided into chemotherapy sensitivity group and chemotherapy resistance group according to the recurrence cases, the clinical expression and survival rate for two groups were compared, the influence factors of survival time were analyzed.Results The positive rate of P53, Livin and PARP for chemotherapy sensitivity group was 47.1%, 56.9%and 52.9%;the positive rate for chemotherapy resistance group was 73.9%, 95.7% and 95.7%,the diyforences were significant(P<0.05).After 1, 3 and 5 years of treatment, the survival rate for chemotherapy sensitivity group was 100.0%, 82.4% and 66.7%,The survival rate for chemotherapy resistance group was 87.0%, 26.1% and 8.7%,the diyforences were significant(P<0.05).Based on the Cox regression model, the influence factors of the patient's age, pathological differentiation degree, clinical staging and chemotherapy sensitivity were introduced.It was known that the patient's survival time was greatly influenced by clinical staging and chemotherapy sensitivity (P<0.05).Conclusion For patients with epithelial ovarian cancer, the expression of P53, Livin and PARP is correlated with chemotherapy resistance.Therefore, the clinical effect is predictable, for patients with higher expression, the personalized therapy can improve the patient's prognosis.

A pilot study of the ERCC1 and XPF genes in forensic age estimation / 中国法医学杂志

Objective The aim of this study is to detect the mRNA and protein expression levels of ERCC1 and XPF genes among different age groups of healthy Chinese Han individuals,and to analyze the correlation between the mRNA and protein expression levels andthe age of individuals in order to find new molecular markers for forensic age estimation.Methods Peripheral blood samples were obtained from 150 unrelated healthy Chinese Han individuals.The plasma was centrifuged from the whole blood by gradient centrifugation,and the totalRNA was extractedwithTrizol fromperipheral blood mononuclear cells(PBMCs).Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to quantitatively analyze the mRNA relative expression levels of ERCC1and XPF in PBMCs.Enzyme linked immunosorbent assay (ELISA) was used to quantitatively analyze the protein expression levels of ERCC1and XPF in plasma.Results There were no significant differences in the mRNA relative expression levels of ERCC1 and XPF in PBMCs between males and females(P＞0.05).Significant differences were found in the mRNA relative expression levels of ERCC1 and XPF between different age groups (P＜0.05).Regression analysis showed thatthe mRNA relative expression levels of ERCC1 and XPF were both negatively correlated with age.The correlation coefficients(r) were-0.578 and-0.844,respectively.When the age was used as independent variable(x) and the mRNA expression relative level as dependent variable (y),the fitting curveswere Y=3.3E-5X2-0.0261X+1.9175 (R2=0.3244,P＜0.01),Y=0.0003X2-0.0459X+2.0439 R2=0.729,P＜0.01),respectively.There were no significant differences inthe protein expression levels of ERCC1 and XPF in plasma between different age groups or genders (P＞0.05).Conclusion The mRNA relative expression levels of ERCC1 and XPF in PBMCsdeclined with the increase of age,however,the protein expression levels in plasma were unrelated to age.ERCC 1 and XPF genes can be used asnew molecular markers for forensic age estimation,so as to providetheoretical basis for establishing the mathematical model of ERCC1/XPF genesin concern ofindividual ages.

Expression and its clinical significance of ERCC1 in stage Ⅱ colorectal carcinoma / 西安交通大学学报(医学版)

Objective To investigate the expression and clinical significance of excision repair cross complementing gene 1 (ERCC1 )in colorectal carcinoma of stage Ⅱ and its clinical significance.Methods We collected 56 cases of stage Ⅱ postoperative colorectal carcinoma tissue and detected ERCC1 expression with immunofluorescence technique.Statistical analysis was made with SPSS13.0 software.Results ERCC1 expression was obviously lower in stage II postoperative colorectal carcinoma tissue than in normal tissue (P =0.01).In cancer tissue,ERCC1 expression in patients with relapse or metastasis was significantly lower than in those without (P =0.002);ERCC1 expression in patients with T3 was significantly higher than those with T4 (P = 0.044).ERCC1 expression had a positive correlation with the overall survival (OS)and disease-free survival (DFS)(both P =0.000).In the group of high ERCC1 expression patients,five-year OS rate and DFS rate between patients who had received oxaliplatin-based adjuvant chemotherapy and those who did not have no significant difference (P =0.351;P =0.465).In the group of low ERCC1 expression patients,five-year OS rate and DFS rate of patients who received oxaliplatin-based adjuvant chemotherapy were significantly higher than those of patients who did not (P =0.015,P =0.02).ERCC1 (P =0.031 )and relapse or metastasis (P =0.009)were independent factors affecting OS;relapse or metastasis (P =0.000)was an independent factor affecting DFS.Conclusion ERCC1 is an independent factor affecting the OS of patients with stage Ⅱ colorectal carcinoma.Patients with low ERCC1 expression have poor prognosis,but they can benefit from oxaliplatin-based adjuvant chemotherapy.

Expression and its clinical significance of ERCC1 in stage Ⅱ colorectal carcinoma / 西安交通大学学报(医学版)

Objective To investigate the expression and clinical significance of excision repair cross complementing gene 1 (ERCC1 )in colorectal carcinoma of stage Ⅱ and its clinical significance.Methods We collected 56 cases of stage Ⅱ postoperative colorectal carcinoma tissue and detected ERCC1 expression with immunofluorescence technique.Statistical analysis was made with SPSS13.0 software.Results ERCC1 expression was obviously lower in stage II postoperative colorectal carcinoma tissue than in normal tissue (P =0.01).In cancer tissue,ERCC1 expression in patients with relapse or metastasis was significantly lower than in those without (P =0.002);ERCC1 expression in patients with T3 was significantly higher than those with T4 (P = 0.044).ERCC1 expression had a positive correlation with the overall survival (OS)and disease-free survival (DFS)(both P =0.000).In the group of high ERCC1 expression patients,five-year OS rate and DFS rate between patients who had received oxaliplatin-based adjuvant chemotherapy and those who did not have no significant difference (P =0.351;P =0.465).In the group of low ERCC1 expression patients,five-year OS rate and DFS rate of patients who received oxaliplatin-based adjuvant chemotherapy were significantly higher than those of patients who did not (P =0.015,P =0.02).ERCC1 (P =0.031 )and relapse or metastasis (P =0.009)were independent factors affecting OS;relapse or metastasis (P =0.000)was an independent factor affecting DFS.Conclusion ERCC1 is an independent factor affecting the OS of patients with stage Ⅱ colorectal carcinoma.Patients with low ERCC1 expression have poor prognosis,but they can benefit from oxaliplatin-based adjuvant chemotherapy.

Relationship between expression of ERCC1 and prognosis of smoking patients with advanced NSCLC / 安徽医科大学学报

Objective To investigate the expression of ERCC1 in smoking patients with advanced non-small cell lung cancer(NSCLC) and its relationship with clinical features and prognosis.Methods The expression of ERCC1 was detected in 96 patients with advanced NSCLC by PCR assay.The clinicopathologic factors, treatment effect and survival time were observed.Results The expression of ERCC1 was related to smoking index(P=0.029), but it was not related to other clinicopathological factors.The patients with low expression of ERCC1 had better response rate and median survival time when compared to those with high expression patients.The difference was statistically significant(P=0.001,P<0.01).Conclusion ERCC1 expression is associated with smoking index and the patients with low expression of ERCC1 shows higher chemotherapy efficiency and longer median survival than patients with high expression, which indicates that detection of ERCC1 may be a useful parameter in evaluating the therapeutic effect and prognosis of smoking patients with advanced NSCLC.

A case of Cockayne syndrome caused by ERCC8 gene mutation / 临床儿科杂志

Objective To explore the clinical,radiological and gene mutation features ofERCC8 gene in one patient with Cockayne syndrome.Methods Clinical and radiological data of a girl diagnosed with Cockayne syndrome through gene detection were retrospectively analyzed.Next-generation sequencing was used to detect genetic cause.Sanger sequencing was used to confirm the candidate variants and detect mutations in her parents and sister.ResuRs The patient showed psychomotor retardation,growth failure,special face,and light sensitivity.Neurological examination revealed noticeable developmental delay,motor impairment,spastic paralysis,and cerebellar ataxia.Brain MRI revealed symmetrical demyelination of bilateral centrum semiovale and periventricular white matter.The cerebellum was atrophic.The patient was found to have compound heterozygous mutations of c.397C＞T(p.Q133X) and c.394_398del(p.L132fs).Sanger sequencing showed these two mutations were inherited from her mother and father respectively.Conclusions Next-generation sequencing technology is a useful tool for the detection of mutation in ERCC8 gene,which is valuable for the diagnosis of Cockayne syndrome.These two mutations expanded the mutation spectrum of Cockayne syndrome in Chinese population.

ERCC1 Expression-Based Randomized Phase II Study of Gemcitabine/Cisplatin Versus Irinotecan/Cisplatin in Patients with Advanced Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We evaluated the clinical utility of excision repair cross-complementation group 1 (ERCC1) expression as a predictive biomarker for platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Eligible patients were randomly assigned to the GP (gemcitabine 1,250 mg/m² on days 1 and 8, and cisplatin 75 mg/m² on day 1 every 3 weeks) or IP (irinotecan 65 mg/m² and cisplatin 30 mg/m² on days 1 and 8 every 3 weeks) arm. The primary goal of this study was to compare the response rate (RR) of the GP and IP arms according to the ERCC1 expression level. RESULTS: A total of 279 patients were randomly assigned to the GP (n=139) and IP (n=140) arms, among which 63% were ERCC1-positive and 268 patients were assessable for the RR. The GP and IP arms did not differ significantly with respect to the RR (29.8% vs. 27.0%, respectively; p=0.082), median progression-free survival (PFS; 4.5 months vs. 3.9 months, respectively; p=0.117), and overall survival (OS; 16.5 months vs. 16.7 months, respectively; p=0.313). When comparing the efficacy between the ERCC1-positive and ERCC1-negative groups, there was no significant difference in the RR (GP, 28.2% vs. 32.6%, respectively, p=0.509; IP, 30.2% vs. 21.6%, respectively, p=0.536), median PFS (GP, 4.6 months vs. 5.0 months, respectively, p=0.506; IP, 3.9 months vs. 3.7 months, respectively, p=0.748), or median OS (GP, 18.6 months vs. 11.9 months, respectively, p=0.070; IP, 17.5 months vs. 14.0 months, respectively, p=0.821). CONCLUSION: Immunohistochemical analysis of the ERCC1 expression level did not differentiate the efficacy of platinum-based chemotherapy in advanced NSCLC.

Association between ERCC2/XPD Polymorphisms and UVC-induced DNA Damage Using Transfected Cells Model / 中国医科大学学报

Objective To explore the function of ERCC2/XPD polymorphisms in the repair of DNA damage induced by UVC. Methods Plas?mids stably expressing ERCC2/XPD rs13181 AA(Lys751)and ERCC2/XPD rs13181 CC(Gln751)were transfected into Chinese hamster ovary cells,and the stable ERCC2 transfected cell lines were obtained. MTT assay was used to compare the inhibitory rates of the transfected cells treated with UVC at different irradiation intensity. The DNA damage repair ability of the transfected cells treated with UVC for 1,3,6 and 24 h was detected by modified comet assay. Results Compared with UV5ERCC2(CC),UV5ERCC2(CC) was more sensitive to UVC with decreased cell viability. DNA damage level of UV5ERCC2(CC) cells was more serious than UV5ERCC2(CC). Conclusion DNA repair capacity of ERCC2/XPD rs13181A allelic is lower than its wild?type,suggesting that ERCC2/XPDpolymorphisms play a critical role in UVC?induced DNA damage repair.

The relationship on polymorphisms of ERCC1-4533/8092 and the susceptibility of hepatocellular carcinoma / 国际检验医学杂志

Objective To investigate the relationship on the excision repair cross complementing gene 1(ERCC1)‐4533/8092 site single nucleotide polymorphisms(SNPs) and the susceptibility to hepatocellular carcinoma(HCC) in Guangxi Zhuang population . Methods Polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method was used to detect the ER‐CC1‐4533/8092 gene polymorphism in 88 cases with primary liver cancer and 82 cases of normal controls .Results There was no difference in the frequency distribution of ERCC1‐4533 in the case group and the control group ,the frequency distribution of the ERCC1‐8092 in the case group and the control group was different(P< 0 .05) .Compared with ERCC1‐8092 CC ,ERCC1‐C8092 CA/AA had higher risk of primary hepatocellular carcinoma(CA :OR=2 .556 ,95% CI:1 .345 -4 .855;AA :OR= 8 .667 ,95% CI:1 .000-75 .092) .ERCC1‐8092 C allele as a reference ,ERCC1‐8092 A allele can increase the risk of primary liver cancer (OR=2 .387 ,95% CI:1 .428-3 .992) .Conclusion The genetic polymorphisms of ERCC1‐8092 sites are associated with susceptibility to hepatocellular carcinoma in Guangxi Zhuang population .

Nucleotide Excision Repair Gene ERCC2 and ERCC5 Variants Increase Risk of Uterine Cervical Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Defects in the DNA damage repair process can cause genomic instability and play an important role in cervical carcinogenesis. The purpose of this study was to analyze the association of 29 candidate single nucleotide polymorphisms (SNPs) in genes in the DNA repair pathway, TP53, and TP53BP1 with the risk of cervical cancer. MATERIALS AND METHODS: Twenty-nine SNPs in four genes in the DNA repair pathway (ERCC2, ERCC5, NBS1, and XRCC1), TP53, and TP53BP1 were genotyped for 478 cervical cancer patients and 922 healthy control subjects, and their effects on cervical carcinogenesis were analyzed. RESULTS: The most significant association was found for rs17655 in ERCC5, with an age-adjusted p-value < 0.0001, for which a strong additive effect of the risk allele C was observed (odds ratio, 2.01 for CC to GG). On the other hand, another significant polymorphism rs454421 in ERCC2 showed a dominant effect (odds ratio, 1.68 for GA+AA to GG) with an age-adjusted p-value of 0.0009. The association of these polymorphisms remained significant regardless of the age of onset. The significant result for rs17655 was also consistent for subgroups of patients defined by histology and human papillomavirus (HPV) types. However, for rs454421, the association was observed only in patients with squamous cell carcinoma and non-HPV 18 type. CONCLUSION: The results of this study show a novel association of cervical cancer and the genes involved in the nucleotide excision pathway in the Korean population.