Candidate germline polymorphisms of genes belonging to the pathways of four drugs used in osteosarcoma standard chemotherapy associated with risk, survival and toxicity in non-metastatic high-grade osteosarcoma

Hattinger, Claudia Maria; Biason, Paola; Iacoboni, Erika; Gagno, Sara; Fanelli, Marilù; Tavanti, Elisa; Vella, Serena; Ferrari, Stefano; Roli, Andrea; Roncato, Rossana; Giodini, Luciana; Scotlandi, Katia; Picci, Piero; Toffoli, Giuseppe; Serra, Massimo

doi:10.18632/oncotarget.11486

Cited by 36 publications

(60 citation statements)

References 34 publications

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“…The study characteristics of the 28 articles included, all were candidate gene studies published between 2008 and 2017, are shown in Table 1 . Most were cohort studies (Wang et al, 2008 ; Filipski et al, 2009 ; Goekkurt et al, 2009 ; Chen et al, 2010 ; Khrunin et al, 2010a , 2012 , 2014 ; KimCurran et al, 2011 ; Tzvetkov et al, 2011 ; Erculj et al, 2012 ; Iwata et al, 2012 ; Windsor et al, 2012 ; Xu et al, 2012 , 2013 ; Zhang and Zhou, 2012 ; Zhang et al, 2012 ; Hinai et al, 2013 ; Khokhrin et al, 2013 ; Lamba et al, 2014 ; Yuan et al, 2015 ; Hattinger et al, 2016 ; Powrozek et al, 2016 ; Chang et al, 2017 ) and none were genome wide association studies (GWAS). Key details of subject characteristics [e.g., ethnicity and inclusion criteria (Sprowl et al, 2012 )], type of chemotherapy regimens (Erculj et al, 2012 ; Sprowl et al, 2012 ; Powrozek et al, 2016 ), and nephrotoxicity criteria (Goekkurt et al, 2009 ; Kim et al, 2012 ; Khrunin et al, 2014 ) were not reported in some studies.…”

Section: Resultsmentioning

confidence: 99%

Genetic Variations and Cisplatin Nephrotoxicity: A Systematic Review

et al. 2018

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Background: Nephrotoxicity is a notable adverse effect in cisplatin treated patients characterized by tubular injury and/or increased serum creatinine (SCr) with incidence varying from 20 to 70%. Pharmacogenomics has been shown to identify strongly predictive genetic markers to help determine which patients are more likely to experience, for example, a serious adverse drug reaction or receive optimal benefit through enhanced efficacy. Genetic variations have been reported to influence the risk of cisplatin nephrotoxicity; however, a comprehensive overview is lacking.Methods: A systematic review was performed using Pubmed, Embase and Web of Science on clinical studies that used cisplatin-based chemotherapy as treatment, had available genotyping data, and evaluated nephrotoxicity as an outcome. The quality of reporting was assessed using the STrengthening the REporting of Genetic Association Studies (STREGA) checklist.Results: Twenty-eight eligible studies were included; all were candidate gene studies. Over 300 SNPs across 135 genes were studied; 29 SNPs in 14 genes were significantly associated with cisplatin-induced nephrotoxicity. A variation in SLC22A2 rs316019, a gene involved in platinum uptake by the kidney, was associated with different measures of nephrotoxicity in four independent studies. Further, variants of ERCC1 (rs11615 and rs3212986) and ERCC2 (rs13181), two genes involved in DNA repair, were found to be positively associated with increased risks of nephrotoxicity in two independent studies.Conclusion: Three genes consistently associated with cisplatin-induced nephrotoxicity. Further research is needed to assess the biological mechanism and the clinical value of modifying treatment based on SLCC22A2 and ERCC1/2 genotypes.

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Section: Resultsmentioning

confidence: 99%

Genetic Variations and Cisplatin Nephrotoxicity: A Systematic Review

et al. 2018

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“…We found 14 studies regarding ERCC polymorphisms, including one meta-analysis and one commentary, both of which were excluded. One study [ 19 ] was excluded due to lack of detailed data. Eleven studies met our criteria and were included in the meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

Meta-analysis showing that ERCC1 polymorphism is predictive of osteosarcoma prognosis

et al. 2017

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To investigate correlations between excision repair cross-complementation group 1 (ERCC1) and 2 (ERCC2) polymorphisms and osteosarcoma prognosis, we conducted a meta-analysis of studies published through October 2016. Studies were identified in the PubMed, ScienceDirect, Springer, and Web of Science databases using preferred reporting items for systematic reviews and meta-analyses (PRISMA). Odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) for overall survival (OS), tumor response (TR), and event-free survival (EFS) were estimated. Our meta-analysis included eleven studies in which four SNPs (ERCC1 rs11615 and rs3212986, ERCC2 rs13181 and rs1799793) reportedly associated with osteosarcoma prognosis were investigated. Each of these studies scored > 6 on the Newcastle-Ottawa Scale (NOS). We found that only one SNP, ERCC1 rs11615, correlated with improved OS and TR. The HR of T vs. C for OS was 1.455 (T/C, 95% CI = 1.151–1.839, P = 0.002, I2 = 37.80%). The OR of T vs. C for good TR was 0.554 (T/C, 95% CI = 0.437–0.702, P < 0.001, I2 = 0%). Few significant outcome was observed in subgroup analyses stratified based on study characteristics with adjustments for potential confounders. Our results suggest that ERCC1 rs11615 CC is associated with a better clinical outcome. This suggests rs11615 may be a useful genetic marker for predicting osteosarcoma prognosis.

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“…However, the prognosis for OS patients remains poor even with the help of chemotherapy because some OS are resistant to chemotherapy and radiation therapy [4-6]. Thus, great efforts have been made to elucidate the mechanisms underlying the invasion and chemo-resistance of OS [7-10]. In specific conditions, the bad sensitivity towards a certain chemotherapy may be resulted from the enhanced anti-apoptotic potentials of the cancer cells [11-13].…”

Section: Introductionmentioning

confidence: 99%

Post-Transcriptional Control of Angiotensin II Type 1 Receptor Regulates Osteosarcoma Cell Death

Zhao

Liu

2018

Cell Physiol Biochem

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Background/Aims: MicroRNAs (miRNAs) play an essential role in the tumorigenesis of osteosarcoma (OS). However, the effects of miR-1248 on chemo-resistant potential of OS have not been studied. Here, we addressed this question. Methods: The levels of miR-1248 and apoptotic protein angiotensin II type 1 receptor (AGTR1) in OS specimens were examined by RT-qPCR and Western blotting, respectively. The relationship between miR-1248 and AGTR1 was determined by analysis of Spearman’s Rank Correlation Coefficients. The patient survival was determined with Kaplan-Meier curves. Bioinformatics analyses were done to predict microRNAs (miRNAs) that target AGTR1. The functional binding of miRNAs to AGTR1 mRNA was examined by a dual luciferase reporter assay. Cell viability was determined by an CCK-8 assay. Apoptosis was determined by a fluorescence-based apoptosis assay. Results: The levels of miR-1248 were significantly elevated while the levels of AGTR1 were significantly decreased in OS specimens than in paired adjacent normal tissue. The levels of miR-1248 were negatively correlated to the levels of AGTR1. Moreover, the patients with high miR-1248 levels had poorer survival than those with low MiR-1248 levels, and the patients with low AGTR1 levels had poorer survival than those with high AGTR1 levels. MiR-1248 inhibited protein translation of AGTR1, through binding to the 3’-UTR of the AGTR1 mRNA. The AGTR1-mediated cell apoptosis was suppressed by overexpressing miR-1248, and was augmented by depleting miR-1248. Conclusion: Increased miR-1248 expression in OS may inhibit AGTR1-mediated cancer cell death in chemotherapy. The outcome of chemotherapy may be improved by the suppression of miR-1248 in OS cells.

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Candidate germline polymorphisms of genes belonging to the pathways of four drugs used in osteosarcoma standard chemotherapy associated with risk, survival and toxicity in non-metastatic high-grade osteosarcoma

Cited by 36 publications

References 34 publications

Genetic Variations and Cisplatin Nephrotoxicity: A Systematic Review

Genetic Variations and Cisplatin Nephrotoxicity: A Systematic Review

Meta-analysis showing that ERCC1 polymorphism is predictive of osteosarcoma prognosis

Post-Transcriptional Control of Angiotensin II Type 1 Receptor Regulates Osteosarcoma Cell Death

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