scholarly journals Meta-analysis of excision repair cross complementary gene 1 (ERCC1) expression and platinum chemosensitivity in patients with ovarian cancer

2020 ◽  
Vol 9 (5) ◽  
pp. 3428-3435
Author(s):  
Jiaohong Wu ◽  
Renliang Li ◽  
Xinyan Chen ◽  
Cong Chen ◽  
Haitang Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Excision Repair ◽  
Meta Analysis ◽  
Complementary Gene ◽  
Ercc1 Expression

scholarly journals ERCC1 expression and platinum chemosensitivity in patients with ovarian cancer: A meta-analysis

2020 ◽  
Vol 35 (4) ◽  
pp. 12-19
Author(s):  
Chunjie Zhang ◽  
Shan Gao ◽  
Jingwen Hou
Keyword(s):  
Ovarian Cancer ◽  
Excision Repair ◽  
Meta Analysis ◽  
Effective Rate ◽  
High Expression ◽  
High Expression Group ◽  
Significant Difference ◽  
Ercc1 Expression ◽  
The Relationship ◽  
Low Expression

Objective: This study aimed to comprehensively investigate the correlation of ERCC1 expression and chemosensitivity of ovarian cancer. Methods: The literature on the relationship between the excision repair cross complementary gene 1 (ERCC1) and the chemosensitivity of ovarian cancer published in PubMed, Web of Science, EMBASE, CNKI, and the China Wanfang database from the establishment of the databases to June 2020 were searched. Chemosensitivity is evaluated by clinical effective rate (complete remission plus partial remission). Statistical analysis was carried out by using Stata 15.1 software. Results: A total of 11 articles met the inclusion criteria, consisting of 758 patients with ovarian cancer. The results showed a significant difference in chemosensitivity between the low expression group and the high expression group of ERCC1 (odds ratio 4.23; 95% confidence interval 2.96, 6.06; P < 0. 01). The same result was shown in the ethnicity subgroup. Conclusion: The chemosensitivity of ovarian cancer patients with a low expression of ERCC1 is better than that of patients with a high expression.

Excision repair cross-complementary group 1 (ERCC1) as a prognostic biomarker in patients (pts) with solid tumors: A meta-analysis on detection methods.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Milena Perez Mak ◽  
Tiago Kenji Takahashi ◽  
Paulo Marcelo Hoff ◽  
Gilberto Castro ◽  
Igor M. L. Snitcovsky
Keyword(s):  
Primary Endpoint ◽  
Excision Repair ◽  
Meta Analysis ◽  
Random Effect ◽  
Secondary Endpoint ◽  
Detection Methods ◽  
Retrospective Nature ◽  
Ercc1 Expression ◽  
Effect Heterogeneity ◽  
Platinum Chemotherapy

e21040 Background: ERCC1 overexpression is associated with better outcomes in some cancers. The best method to assess its expression, immunohistochemistry (IHC) or polymerase chain reaction (PCR), is not established. To clarify such question, this meta-analysis was conducted. Methods: PUBMED, EMBASE and Cochrane databases were searched with terms: “ERCC1” and “IHC” and/or “PCR” and/or “mRNA”. Inclusion criteria: full papers in English, solid tumor pts, ERCC1 evaluated by IHC and PCR on the same samples, reported correlation between ERCC1 expression and overall survival (OS) – the primary endpoint. As secondary endpoint, correlation between IHC and PCR expression was assessed. Exclusion criteria: review articles and no reported endpoint. Two authors reviewed and classified all papers. Pooled HR and variance were calculated by standard methods, using CMA v2.2.064 (Englewood, USA). Results: 25 articles were retrieved, with 4 included for the primary endpoint (224 pts) and 4 (191) for the secondary endpoint. All were retrospective, with diverse primary sites. Except for one, platinum chemotherapy was employed. All studies used 8F1 clone, and in 2, FL297 clone was also evaluated. ERCC1 positivity was determined by H-score in 2 studies and by AQUA in 2. mRNA ERCC1 positivity was variably defined. In general, ERCC1 overexpression was correlated with longer OS (HR 0.569, 95% CI 0.436 - 0.743, p <0.001). Similar results were found in terms of OS either by IHC or PCR (HR 0.626, 95% CI 0.46 – 0.853, p 0.003 and HR 0.434, 95% CI 0.257 – 0.730, p 0.002; respectively). No correlation between IHC and PCR overexpression was found (coefficient 0.098 p 0.444, random effect). Heterogeneity was detected only in IHC analysis, when expression was detected by both FL297 and 8F1 antibodies (p 0.001, fixed effect). Conclusions: ERCC1 overexpression is associated with better OS, regardless of employed methodology. However, protein and mRNA expression are not correlated. Major limitations to our analysis include the variety of employed ERCC1 detection methods and retrospective nature of data. Definitive conclusions on the prognostic role of ERCC1 and best methodology remain to be answered.

scholarly journals ERCC1-Positive Circulating Tumor Cells in the Blood of Ovarian Cancer Patients as a Predictive Biomarker for Platinum Resistance

2014 ◽  
Vol 60 (10) ◽  
pp. 1282-1289 ◽  
Author(s):  
Jan Dominik Kuhlmann ◽  
Pauline Wimberger ◽  
Agnes Bankfalvi ◽  
Thomas Keller ◽  
Sarah Schöler ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Surface ◽  
Cancer Patients ◽  
Independent Predictor ◽  
Excision Repair ◽  
Complementation Group ◽  
Primary Diagnosis ◽  
Platinum Resistance ◽  
Ercc1 Expression ◽  
Group 1

Abstract BACKGROUND Platinum resistance constitutes one of the most recognized clinical challenges for ovarian cancer. Notably, the detection of the primary tumor-based excision repair cross-complementation group 1 (ERCC1) protein by immunohistochemistry was recently shown to be inaccurate for the prediction of platinum resistance. On the basis of the previous finding that circulating tumor cells (CTC) in the blood of ovarian cancer patients are prognostically significant, and given our hypothesis that the negative prognostic impact of CTC may arise from a cellular phenotype associated with platinum resistance, we asked whether expression of the excision repair cross-complementation group 1 (ERCC1) gene in the form of the ERCC1 transcript in CTC may be a suitable blood-based biomarker for platinum resistance. METHODS The presence of CTC was analyzed by immunomagnetic CTC enrichment (n = 143 patients) targeting the epithelial epitopes epithelial cell adhesion molecule (EPCAM) (also known as GA733-2) and mucin 1, cell surface associated (MUC1), followed by multiplex reverse-transcription PCR to detect the transcripts EPCAM, MUC1, and mucin 16, cell surface associated (MUC16) (also known as CA125), including ERCC1 transcripts in a separate approach. ERCC1 expression in primary tumors was comparatively assessed by immunohistochemistry, using the antibody 8F1. RESULTS At primary diagnosis, the presence of CTC was observed in 14% of patients and constituted an independent predictor of overall survival (OS) (P = 0.041). ERCC1-positive CTC (ERCC1+CTC) were observed in 8% of patients and constituted an independent predictor, not only for OS but also for progression-free survival (PFS) (P = 0.026 and P = 0.009, respectively). More interestingly, we discovered the presence of ERCC1+CTC at primary diagnosis to be likewise an independent predictor of platinum resistance (P = 0.010), whereas ERCC1 expression in corresponding primary tumor tissue predicted neither platinum resistance nor prognosis. CONCLUSIONS The presence of ERCC1+CTC can serve as a blood-based diagnostic biomarker for predicting platinum resistance at primary diagnosis of ovarian cancer.

ERCC1 as a prognostic factor for survival in patients with advanced urothelial cancer treated with platinium-based chemotherapy: A systematic review and meta-analysis.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 351-351
Author(s):  
Yuksel Urun ◽  
Jeffrey J. Leow ◽  
Andre Poisl Fay ◽  
Laurence Albiges ◽  
Toni K. Choueiri ◽  
...  
Keyword(s):  
Systematic Review ◽  
Urothelial Cancer ◽  
Excision Repair ◽  
Meta Analysis ◽  
Expression Level ◽  
Cochrane Central Register ◽  
Moderate Amount ◽  
Study Heterogeneity ◽  
Advanced Urothelial Cancer ◽  
Ercc1 Expression

351 Background: Platinium based chemotherapy (CT) is an essential part in the treatment of advanced urothelial cancer (AUC). However, not all patients derive benefit. A body of evidence suggests that excision repair cross-complementation group 1 (ERCC1) expression level may correlate with outcome in platinum treated patients. We thought to perform a systematic review and meta-analysis to better elucidate its role in AUC. Methods: A comprehensive literature review was performed to identify all studies comparing platinum-based regimens according to expression levels of ERCC1 for patients with AUC. The search included the PubMed, Embase, Cochrane Central Register of Controlled Trials databases, and abstracts from the American Society of Clinical Oncology meetings up to June 2014. Pooled analyses were conducted using fixed and random effects models. Results: A total of 554 patients included in eight studies were evaluated. ERCC1 expression was positive in 270 (49%) patients and negative in 284 (51%) patients. The median age of patients was 63 years. The overall survival (OS) was significantly better in patients with negative ERCC1 expression (pooled hazard ratio (HR) 1.90 (95% confidence interval [CI], 0.98–3.67; p=0.006). There was moderate amount of between-study heterogeneity present (I-square 70%). Conclusions: This study's findings support the hypothesis that low ERCC1 expression is associated with benefit from cisplatin-based treatment. The substantial amount of between-study heterogeneity may indicate the need for standardized methods to classify ERCC1 expression level. Prospective studies are necessary to determine the role of ERCC1 levels for treatment selection in patients with AUC.

Prediction of response to chemotherapy by ERCC1 immunohistochemistry and ERCC1 polymorphism in ovarian cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5568-5568
Author(s):  
K. D. Steffensen ◽  
M. Waldstrøm ◽  
U. Jeppesen ◽  
I. Brandslund ◽  
A. Jakobsen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Repair ◽  
Epithelial Ovarian Cancer ◽  
Dna Adducts ◽  
Excision Repair ◽  
Snp Genotyping ◽  
Repair Capacity ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Ercc1 Expression

5568 Background: The response of tumor cells to platinum-based drugs involves DNA repair mechanisms. Platinum-DNA adducts are repaired by nucleotide excision repair (NER) enzymes that recognize the DNA damage and excise the platinum-DNA adducts from the injured DNA strand. Excision repair cross-complementation group 1 (ERCC1) is one of the genes that encode the proteins of the NER complex and several studies have linked ERCC1 to platinum resistance in cell lines and in human cancers. Cells with a high repair capacity, e.g. high level of ERCC1 expression may therefore be resistant to platinum-based chemotherapy, and conversely, polymorphisms within encoding DNA repair enzymes or low repair capacity may confer sensitivity. A common single nucleotide polymorphism (SNP) of ERCC1 at codon 118 have been proposed to impair ERCC1 translation and reduce ERCC1 protein expression and consequently influence the response to platinum based chemotherapy. The aim of this study was to evaluate ERCC1 expression and ERCC1 118 polymorphism in epithelial ovarian cancer and the potential association with response to platinum-based chemotherapy. Methods: Formalin-fixed, paraffin-embedded tissue sections from 159 patients with epithelial ovarian cancer, FIGO stage IIb-IV, were used for immunohistochemistry (monoclonal mouse antibody, clone 8F1, Neomarkers). ERCC1 codon 118 SNP genotyping was performed by real time PCR, Taqman SNP genotyping assay. Results: ERCC1 protein overexpression was found in 37.7 % of the tumors. The response rate (normalization of CA125 during platinum-based chemotherapy) was 63.6 % (35/55) in patients with ERCC1-negative tumors compared to only 35.6 % (16/45) in patients with ERCC1-positive tumors. (p = 0.0052, χ2). Furthermore increasing immunohistochemical score (H-score) was associated with poorer response to chemotherapy. (p = 0.0006, Spearman`s). The T/T genotype (44 %) showed better response to chemotherapy than C/C + C/T (15 % + 41 %) variants (p=0.042). Conclusions: Patients with ERCC1-negative tumors appear to have significantly better response to platinumbased chemotherapy compared to patients with ERCC1-positive tumors. In addition the TT genotype seems to be favorable towards better response to platinum-based chemotherapy. No significant financial relationships to disclose.

ERCC1 Genotype and Phenotype in Epithelial Ovarian Cancer Identify Patients Likely to Benefit From Paclitaxel Treatment in Addition to Platinum-Based Therapy

2007 ◽  
Vol 25 (33) ◽  
pp. 5172-5179 ◽  
Author(s):  
Stephanie Smith ◽  
Dan Su ◽  
Irene A. Rigault de la Longrais ◽  
Peter Schwartz ◽  
Manuela Puopolo ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Disease Progression ◽  
Treatment Response ◽  
Cancer Patients ◽  
Excision Repair ◽  
Platinum Resistance ◽  
Platinum Based Chemotherapy ◽  
Risk Of Disease ◽  
Ercc1 Expression

Purpose To investigate the effect of excision repair cross-complementation group 1 (ERCC1) on treatment response and survival of patients treated with platinum chemotherapy with or without paclitaxel. Patients and Methods Tumor samples from epithelial ovarian cancer patients were evaluated for ERCC1 mRNA expression and a single nucleotide polymorphism at codon 118 (C>T). Of 178 patients treated with postoperative platinum-based chemotherapy, 75 were also given paclitaxel. For all of these patients, ERCC1 expression and genotype were analyzed for associations with treatment response and survival. Results Among the 103 patients treated with platinum without paclitaxel, the C/C genotype, compared with C/T and T/T, was associated with greater risk of disease progression and death (hazard ratio [HR], 1.95, P = .051; HR, 2.01, P = .033, respectively); high levels of ERCC1 mRNA, compared with low levels, were associated with greater risk of disease progression (HR, 2.41; P = .014). Similarly, when the ERCC1 data were combined, patients with the C/C genotype and high ERCC1 expression had greater risk for disease progression (HR, 3.73; P = .003) compared with those with low expression and non-C/C genotype. However, for the 75 patients treated with platinum plus paclitaxel, the C/C genotype and high ERCC1 expression were not associated with poor prognosis, suggesting that paclitaxel may help to alleviate ERCC1-related platinum resistance. Conclusion Ovarian cancer patients with high ERCC1 expression or the C/C genotype at codon 118 may benefit from the combination of platinum and paclitaxel, while those with low ERCC1 expression or the C/T or T/T genotype may respond well to platinum without paclitaxel.

scholarly journals FEN1 Blockade for Platinum Chemo-Sensitization and Synthetic Lethality in Epithelial Ovarian Cancers

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1866
Author(s):  
Katia A. Mesquita ◽  
Reem Ali ◽  
Rachel Doherty ◽  
Michael S. Toss ◽  
Islam Miligy ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
High Throughput Screening ◽  
Nuclear Translocation ◽  
Synthetic Lethality ◽  
Excision Repair ◽  
Progression Free Survival ◽  
Ovarian Cancer Cells ◽  
Physical Interaction ◽  
Base Excision

FEN1 plays critical roles in long patch base excision repair (LP-BER), Okazaki fragment maturation, and rescue of stalled replication forks. In a clinical cohort, FEN1 overexpression is associated with aggressive phenotype and poor progression-free survival after platinum chemotherapy. Pre-clinically, FEN1 is induced upon cisplatin treatment, and nuclear translocation of FEN1 is dependent on physical interaction with importin β. FEN1 depletion, gene inactivation, or inhibition re-sensitizes platinum-resistant ovarian cancer cells to cisplatin. BRCA2 deficient cells exhibited synthetic lethality upon treatment with a FEN1 inhibitor. FEN1 inhibitor-resistant PEO1R cells were generated, and these reactivated BRCA2 and overexpressed the key repair proteins, POLβ and XRCC1. FEN1i treatment was selectively toxic to POLβ deficient but not XRCC1 deficient ovarian cancer cells. High throughput screening of 391,275 compounds identified several FEN1 inhibitor hits that are suitable for further drug development. We conclude that FEN1 is a valid target for ovarian cancer therapy.

scholarly journals Comparison of the survival outcomes of laparoscopy versus laparotomy in treatment of early-stage ovarian cancer: a systematic review and meta-analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qingduo Kong ◽  
Hongyi Wei ◽  
Jing Zhang ◽  
Yilin Li ◽  
Yongjun Wang
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Cochrane Library ◽  
Survival Outcomes ◽  
Free Survival ◽  
Review Manager ◽  
Early Stage Ovarian Cancer

Abstract Background Laparoscopy has been widely used for patients with early-stage epithelial ovarian cancer (eEOC). However, there is limited evidence regarding whether survival outcomes of laparoscopy are equivalent to those of laparotomy among patients with eEOC. The result of survival outcomes of laparoscopy is still controversial. The aim of this meta-analysis is to analyze the survival outcomes of laparoscopy versus laparotomy in the treatment of eEOC. Methods According to the keywords, Pubmed, Embase, Cochrane Library and Clinicaltrials.gov were searched for studies from January 1994 to January 2021. Studies comparing the efficacy and safety of laparoscopy versus laparotomy for patients with eEOC were assessed for eligibility. Only studies including outcomes of overall survival (OS) were enrolled. The meta-analysis was performed using Stata software (Version 12.0) and Review Manager (Version 5.2). Results A total of 6 retrospective non-random studies were included in this meta-analysis. The pooled results indicated that there was no difference between two approaches for patients with eEOC in OS (HR = 0.6, P = 0.446), progression-free survival (PFS) (HR = 0.6, P = 0.137) and upstaging rate (OR = 1.18, P = 0.54). But the recurrence rate of laparoscopic surgery was lower than that of laparotomic surgery (OR = 0.48, P = 0.008). Conclusions Laparoscopy and laparotomy appear to provide comparable overall survival and progression-free survival outcomes for patients with eEOC. Further high-quality studies are needed to enhance this statement.

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