Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

Chen, Juan; Wang, Zhan; Zou, Ting; Cui, Jiajia; Zheng, Wei; Jiang, Weixiong; Zhou, Hong‐Hao; Liu, Zhao‐Qian

doi:10.18632/oncotarget.9688

Cited by 15 publications

(16 citation statements)

References 66 publications

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“…Similarly, earlier reports from the University of Oklahoma Health Science Center, USA, revealed a higher rate of platinum-resistant (58%) compared to sensitive patients (42%) (Moxley et al, 2013). In line with this, another independent study in China showed 76.8% of patients resistant to different combinations of platinum-based therapy (Chen et al, 2016). In contrast, studies including Asian, Caucasian EOC patients demonstrated the lower frequency of nonresponder against platinum-based chemotherapy (Tang, Lyu, Zhang, & Liu, 2017).…”

Section: Discussionsupporting

confidence: 57%

Role of common ERCC1 polymorphisms in cisplatin‐resistant epithelial ovarian cancer patients: A study in Chinese cohort

Bao

Yang

Zhao

et al. 2020

Int J Immunogenetics

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Epithelial ovarian cancer (EOC) contributes the majority of death cases among various ovarian malignancies. Although a standard method of treatment is the surgical removal of malignant tissue followed by platinum‐based chemotherapy, a group of patients does not respond appropriately to cisplatin. An appropriate response to cisplatin has been linked with the nucleotide excision repair mechanism. The present study aims to investigate the role of polymorphisms in DNA repair genes, excision repair cross‐complementation group 1 (ERCC1) with susceptibility to EOC development and tumour response to platinum‐based chemotherapy in Chinese EOC patients. Patients (n = 559) reporting to the Department of Oncology and general surgery, the First Affiliated Hospital of Kunming Medical University, were enrolled in the study. Three hundred twenty‐three healthy controls hailing from similar geographical areas without a history of cancer enrolled as healthy controls. Excision repair cross‐complementation group 1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were genotyped by appropriate methods. Distribution of genotypes and allele for ERCC1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were comparable among healthy controls and EOC patients. Interestingly, homozygous mutant and the minor allele for rs11615 and rs3212986 polymorphisms were significantly higher in nonresponder EOC patients when compared to those with a proper response to cisplatin treatment. The prevalence of other SNPs was comparable among the two treated clinical categories. Furthermore, combined genotype revealed significant association of rs11615: TT/ rs3212986: AA genotype combination with cisplatin nonresponder. Variants of rs11615, rs3212986 polymorphisms are associated with cisplatin resistance in Chinese EOC patients. Combined rs11615 and rs3212986 genotypes can be used as a predictive biomarker for platinum‐based chemotherapy outcomes.

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Section: Discussionsupporting

confidence: 57%

Role of common ERCC1 polymorphisms in cisplatin‐resistant epithelial ovarian cancer patients: A study in Chinese cohort

Bao

Yang

Zhao

et al. 2020

Int J Immunogenetics

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“…On the other hand, most studies have focused on protein expression, and the value of ATP7B gene polymorphisms has not been fully addressed. It has been shown that single nucleotide polymorphisms (SNPs) might affect gene expression and function, accounting for interindividual differences in drug efficacy and toxicity 18 , 19 . A few ATP7B SNPs have been reported possible role in chemotherapeutic toxicity 20 , 21 .…”

Section: Introductionmentioning

confidence: 99%

Gene expression and single nucleotide polymorphism of ATP7B are associated with platinum-based chemotherapy response in non-small cell lung cancer patients

Li¹,

Chen²,

Yin³

et al. 2018

J. Cancer

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Objectives: Platinum-based chemotherapy is first-line treatment for non-small cell lung cancer (NSCLC) patients. The efficacy is limited by drug resistance. Recent studies suggest that ATP7B, a copper efflux transporter, may be involved in platinum resistance. However, the clinical significance of ATP7B expression in NSCLC is controversial. Moreover, the effects of single nucleotide polymorphisms (SNPs) in ATP7B gene on the response to platinum-based chemotherapy are scarcely understood. The aim of our study is to evaluate the clinical value of ATP7B in NSCLC patients and explore the interrelationships between ATP7B SNPs and protein expression, and their association with chemotherapy response.Materials and Methods: A total of 247 NSCLC patients were recruited in this study. Among them, 158 patients who received platinum-based chemotherapy were used to explore the interrelationships between ATP7B SNPs, protein expression and chemotherapy response, while 89 patients who underwent surgical resection were used to further investigate the association between ATP7B SNPs and expression level. We genotyped 15 SNPs of ATP7B by Sequenom MassARRAY and determined ATP7B protein levels by immunohistochemistry.Results: Patients with ATP7B-negative tumors had improved chemotherapeutic response (p=0.025) and better overall survival (p=0.044) compared with the patients with ATP7B-positive tumors. The multivariate Cox regression analysis revealed that ATP7B expression was an independent prognostic factor (HR=0.639, 95%CI=0.424-0.962, p=0.032). Moreover, we found that the rs9526814 GG genotype was significantly associated with favorable response to platinum-based chemotherapy when compared with TT+TG genotypes (OR=0.362, 95CI%=0.140-0.935, p=0.036). Mechanistically, rs9526814 GG genotype showed a strong trend towards reduced expression level of ATP7B compared with the TT+TG genotypes (p= 0.048).Conclusion: Our findings indicate that ATP7B rs9526814 may contribute to platinum resistance by influencing ATP7B gene expression and can be used as a potential biomarker to predict the sensitivity of platinum-based chemotherapy in NSCLC patients.

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“…11,12 Over 50% of cancer patients receive platinum agents worldwide. 13 Platinum are particularly effective in bladder and testicular cancers. 14,15 Although widely used in other cancer types such as colon and ovarian, their response rate is stymied by recurrence due to acquired and innate mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Cancer cell-selective modulation of mitochondrial respiration and metabolism by potent organogold(iii) dithiocarbamates

2020

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Pharmacogenomics of platinum-based chemotherapy response in NSCLC: a genotyping study and a pooled analysis

Cited by 15 publications

References 66 publications

Role of common ERCC1 polymorphisms in cisplatin‐resistant epithelial ovarian cancer patients: A study in Chinese cohort

Role of common ERCC1 polymorphisms in cisplatin‐resistant epithelial ovarian cancer patients: A study in Chinese cohort

Gene expression and single nucleotide polymorphism of ATP7B are associated with platinum-based chemotherapy response in non-small cell lung cancer patients

Cancer cell-selective modulation of mitochondrial respiration and metabolism by potent organogold(iii) dithiocarbamates

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