ERCC1 mRNA expression is associated with the clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy

Zhang, H; Li, Jinping; Zhang, Y; Sun, Mengqi; Zhao, Pu; Zhang, G; Jin, ChaoYu; Sun, Liping; He, Max M.; Wang, B; Zhang, X

doi:10.4238/2014.december.4.16

Cited by 3 publications

(3 citation statements)

References 24 publications

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“…In multivariate analysis, after adjusting for prognostic factors including mitotic index, TOP2A expression failed to be a significant independent prognostic parameter. TOP2A is a marker of cell proliferation (Zhang et al 2014) and the direct correlation of this enzyme expression with the mitotic count (although not significant) could account for its failure to be an independent prognostic parameter.…”

Section: Discussionmentioning

confidence: 99%

Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer

Roca¹,

Berruti²,

Sbiera³

et al. 2017

Endocrine-Related Cancer

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Topoisomerase II alpha (TOP2A) and thymidylate synthase (TS) are known prognostic parameters in several tumors and also predictors of efficacy of anthracyclines, topoisomerase inhibitors and fluoropirimidines, respectively. Expression of and mRNA was assessed in 98 patients with adrenocortical carcinoma (ACC) and protein expression was assessed by immunohistochemistry in a subset of 39 tumors. Ninety-two patients were radically resected for stage II-III disease and 38 of them received adjuvant mitotane. Twenty-six patients with metastatic disease received the EDP-M (etoposide, doxorubicin, Adriamycin, cisplatin plus mitotane). and expression in ACC tissue was directly correlated with the clinical data. Both markers were not associated with either disease free survival (DFS) or overall survival (OS) in multivariate analyses and failed to be associated to mitotane efficacy. Disease response or stabilization to EDP-M treatment was observed in 12/17 (71%) and 1/9 (11%) patients with high and low TOP2A expressing tumors ( = 0.0039) and 9/13 (69%) and 4/13 (31%) patients with high and low TS expressing ACC, respectively ( = 0.049). High TOP2A expression was significantly associated with longer time to progression (TTP) after EDP-M. TOP2A and TS proteins assessed by immunohistochemistry significantly correlated with mRNA expression. Immunohistochemical TOP2A expression was associated with a non-significant better response and longer TTP after EDP-M. TOP2A and TS were neither prognostic nor predictive of mitotane efficacy in ACC patients. The predictive role of TOP2A expression of EDP-M activity suggests a significant contribution of Adriamycin and etoposide for the efficacy of the EDP scheme.

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Section: Discussionmentioning

confidence: 99%

Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer

Roca¹,

Berruti²,

Sbiera³

et al. 2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

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“…Twenty‐eight studies met our eligibility criteria; Figure shows the PRISMA flow diagram. These reports spanned 12 years of published research; properties of our sample are shown in Table . This study sample reflects 4,311 patient samples (2,295 tested for protein expression and 2,016 for mRNA) in total.…”

Section: Resultsmentioning

confidence: 99%

The Challenges of Validating in Precision Medicine: The Case of Excision Repair Cross-Complement Group 1 Diagnostic Testing

2017

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Personalized medicine relies upon the successful identification and translation of predictive biomarkers. Unfortunately, biomarker development has often fallen short of expectations. To better understand the obstacles to successful biomarker development, we systematically mapped research activities for a biomarker that has been in development for at least 12 years: excision repair cross-complement group 1 protein (ERCC1) as a biomarker for predicting clinical benefit with platinum-based chemotherapy in non-small cell lung cancer. We found that although research activities explored a wide range of approaches to ERCC1 testing, there was little replication or validation of techniques, and design and reporting of results were generally poor. Our analysis points to problems with coordinating and standardizing research in biomarker development. Clinically meaningful progress in personalized medicine will require concerted efforts to address these problems. In the interim, health care providers should be aware of the complexity involved in biomarker development, cautious about their near-term clinical value, and conscious of applying only validated diagnostics in the clinic. The Oncologist 2017;22:89-96 Implications for Practice: Many hospitals, policy makers, and scientists have made ambitious claims about the promise of personalizing cancer care. When one uses a case example of excision repair cross-complement group 1 protein-a biomarker that has a strong biological rationale and that has been researched for 12 years-the current research environment seems poorly suited for efficient development of biomarker tests. The findings provide grounds for tempering expectations about personalized cancer care-at least in the near term-and shed light on the current gap between the promise and practice of personalized medicine.

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“…Many researchers 16 - 20 found that the expression of ERCC1 was associated with the clinical outcome of NSCLC treated with platinum-based chemotherapy. In a study conducted by Zhang et al 21 among 297 advanced stage NSCLC patients who were treated with platinum-based chemotherapy, it was found that ERCC1 mRNA expression levels in blood were related to the treatment response and survival time. Patients with low ERCC1 mRNA expression level in blood had a significantly higher rate of CR to chemotherapy, with an odds ratio (OR) of 1.56 (95%CI: 1.03-2.47).…”

Section: Discussionmentioning

confidence: 99%

ERCC1_202 Is A Prognostic Biomarker in Advanced Stage Non-Small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy

et al. 2017

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Purpose: To develop a qPCR method to examine the 202 isoform of excision repair cross-complementation group 1 (ERCC1_202) and to evaluate its clinical utility as a predictive biomarker for platinum-based chemotherapy in non-small cell lung cancer (NSCLC).Methods: The relative complementary DNA (cDNA) quantification for ERCC1_202 was conducted using a fluorescence-based, real-time detection method and β-actin was used as a reference gene.Results: A strong correlation was observed between ERCC1_202 mRNA and ERCC1 mRNA levels in NSCLC cells (P < 0.001). 28 patients completed this research. Our results implied that as ERCC1_202 levels increased, the risk of progression (HR = 4.296, P = 0.011) and death (HR = 6.503, P = 0.001) increased. At multivariate analysis, high expression of ERCC1_202 was shown to be an independent predictive factor for time to progression (P = 0.047), and progression-free survival (P = 0.014). However, the high expression of ERCC1_202 was not an independent predictive factor for response (P = 0.324).Conclusions: This study suggests that the efficacy of platinum-based chemotherapy can be improved when customized according to the expression of ERCC1_202.

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ERCC1 mRNA expression is associated with the clinical outcome of non-small cell lung cancer treated with platinum-based chemotherapy

Cited by 3 publications

References 24 publications

Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer

Topoisomerase 2α and thymidylate synthase expression in adrenocortical cancer

The Challenges of Validating in Precision Medicine: The Case of Excision Repair Cross-Complement Group 1 Diagnostic Testing

ERCC1_202 Is A Prognostic Biomarker in Advanced Stage Non-Small Cell Lung Cancer Patients Treated with Platinum-Based Chemotherapy

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