Prostate Cancer Risk in Relation to a Single Nucleotide Polymorphism in the Insulin-like Growth Factor-binding Protein-3 (IGFBP3) Gene: a Meta-analysis

Mao, Yuliang; Xu, Xin; Lin, Yiwei; Chen, Hong; Hu, Zhenghui; Xu, Xianglai; Zhu, Yi; Wu, Jian; Zheng, Xiangyi; Qin, Jie; Xie, Liping

doi:10.7314/apjcp.2012.13.12.6299

Cited by 5 publications

(7 citation statements)

References 39 publications

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“…Our findings taken together with clinical evidence that IGFBP3 promoter polymorphism contributes to prostate cancer risk [ 54 , 55 ], and its potential biomarker value in prostate cancer patients [ 56 ], support the clinical significance of IGFBP3. This study enhances our understanding of a new dynamic in the prostate tumor stroma involving IGFBP3 as an EMT regulator, and its impact on the therapeutic response of cancer epithelial cells.…”

Section: Discussionsupporting

confidence: 76%

Reversion of epithelial-mesenchymal transition by a novel agent DZ-50 via IGF binding protein-3 in prostate cancer cells

2017

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Dysregulation of transforming growth factor-β1 (TGF-β1) and insulin-like growth factor (IGF) axis has been linked to reactive stroma dynamics in prostate cancer progression. IGF binding protein-3 (IGFBP3) induction is initiated by stroma remodeling and could represent a potential therapeutic target for prostate cancer. In previous studies a lead quinazoline-based Doxazosin® derivative, DZ-50, impaired prostate tumor growth by targeting proteins involved in focal adhesion, anoikis resistance and epithelial-mesenchymal-transition (EMT). This study demonstrates that DZ-50 increased expression of the epithelial marker E-cadherin, and decreased the mesenchymal marker N-cadherin in human prostate cancer cells. In DU-145 cells, the effect of DZ-50 on EMT towards mesenchymal epithelial transition (MET) was inhibited by talin1 overexpression, a focal adhesion regulator promoting anoikis resistance and tumor invasion. DZ-50 treatment of human prostate cancer cells and cancer-associated fibroblasts (CAFs) downregulated IGFBP3 expression at mRNA and protein level. In TGF-β1 responsive LNCaPTβRII, TGF-β1 reversed DZ-50-induced MET by antagonizing the drug-induced decrease of nuclear IGFBP3. Furthermore, co-culture with CAFs promoted prostate cancer epithelial cell invasion, an effect that was significantly inhibited by DZ-50. Our findings demonstrate that the lead compound, DZ-50, inhibited the invasive properties of prostate cancer epithelial cells by targeting IGFBP3 and mediating EMT conversion to MET. This study integrated the mechanisms underlying the effect of DZ-50 and further supported the therapeutic value of this compound in the treatment of advanced metastatic prostate cancer.

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Section: Discussionsupporting

confidence: 76%

Reversion of epithelial-mesenchymal transition by a novel agent DZ-50 via IGF binding protein-3 in prostate cancer cells

2017

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“…They suggested that significantly increased risk of PCa was associated with low circulating IGFBP3 levels in the hospital-based control group. 35 , 36 Interestingly, in this meta-analysis, the outcomes were contrary. Therefore, a better method is required to analyze and understand the associations between IGFBP3 polymorphisms and the risk of PCa.…”

Section: Discussionmentioning

confidence: 58%

Association between insulin-like growth factor-binding protein-3 polymorphism -202 A/C and the risk of prostate cancer: a meta-analysis

Qin¹,

Li²,

Tang³

et al. 2016

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BackgroundSome previous studies have investigated the relationship between insulin-like growth factor-binding protein-3 polymorphism and prostate cancer (PCa) susceptibility; however, the findings from those studies remain inconsistent. Hence, the aim of this meta-analysis was to provide a more reliable conclusion about such associations.MethodsA meta-analysis based on twelve studies was conducted, and 8,341 PCa cases and 7,734 controls were included in this analysis. All relevant studies published till February 1, 2016, were identified by searching the databases such as PubMed, EMBASE, and Web of Science. Data were pooled by odds ratios (ORs) with 95% confidence intervals (CIs) in order to assess the strength of such associations. Publication bias was evaluated using Begg’s funnel plots and Egger’s regression test.ResultsSeveral articles provided data only for particular genotypes; therefore, only dominant model analyses were carried out for all of these studies. Initially, the results from this analysis indicated that rs2854744 was not associated with PCa susceptibility (OR=1.12, 95% CI=0.996–1.2). However, after excluding one study due to its heterogeneity and publication bias, a significant relationship was detected between rs2854744 and PCa risk (OR=1.10, 95% CI=1.03–1.17). When stratified by genotyping method, significant results were detected only in the Sequenom method group (OR=1.13, 95% CI=1.04–1.22). Moreover, the results from a subgroup analysis that was conducted by using source of controls were significant only in the population-based control group.ConclusionThis meta-analysis suggested that the insulin-like growth factor-binding protein-3 polymorphism-202 A/C was associated with PCa susceptibility.

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“…Recently, two meta-analyses have reported the correlation between the IGFBP3 -202A/C polymorphism and PCa risk, but there are many differences between their outcomes. The study by Mao et al, 25 including 9,238 cases and 8,741 controls, revealed that IGFBP3 A-202C polymorphisms seemed to increase the risk of PCa, but the effect was not significant. The meta-analysis by Ding et al, 24 which was based on 4,602 PCa cases and 4,880 controls from 16 case–control studies, found a significant association between IGFBP3 A-202C polymorphisms and PCa risk.…”

Section: Discussionmentioning

confidence: 94%

“…Moreover they got different conclusions about the association between IGFBP3 -202A/C polymorphism and PCa risk in race subgroup comparisons. Mao et al 25 reported that the association of –202A/C polymorphism with PCa risk was observed only in Caucasians in the heterozygous codominant model (OR =1.14, 95% CI: 1.05–1.24). In contrast, Ding et al 24 reported that the IGFBP3 -202A/C polymorphism was associated with a significantly decreased risk of PCa in Asians, but not in Europeans or African Americans.…”

Section: Discussionmentioning

confidence: 99%

“…Although quite a few studies investigated the association between IGFBP3 -202A/C polymorphism and PCa risk, 13 – 23 the results from these studies are controversial and inconsistent, and a couple of meta-analyses have been performed to assess the risk of PCa associated with IGFBP3 -202A/C polymorphism by using previously published case–control studies. 24 , 25 But their outcomes still varied leading to controversy. In light of that, a number of new cases have been added since the last comprehensive analysis, and hence we feel necessary to perform an updated meta-analysis to examine the association between the IGFBP3 -202A/C polymorphism and PCa risk.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphism in <em>IGFBP3</em> gene is associated with prostate cancer risk: an updated meta-analysis

Qie

Nian

Liu

et al. 2016

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ObjectiveInsulin-like growth factor-binding protein-3 (IGFBP3) is the major protein that binds with insulin-like growth factor-1 (IGF-1) and is considered to be involved in the development and progression of various cancers. We aimed to examine the association between prostate cancer (PCa) and the IGFBP3 gene-202A/C polymorphism.MethodsA comprehensive search within PubMed, EMBASE, and Cochrane Library was conducted to identify all case–control studies up to October 30, 2015, for a meta-analysis. Pooled odds ratios (ORs) and the 95% confidence intervals (CIs) were calculated using the fixed or random effects model.ResultsEighteen studies including 10,538 cases and 10,078 controls were identified. Overall, the CC genotype of IGFBP3-202A/C polymorphism was associated with increased risk of PCa in homozygote comparison (CC vs AA − OR =1.16, 95% CI: 1.08–1.25) and in recessive model (CC vs AA+AC − OR =1.11, 95% CI: 1.04–1.17). In dominant model, the CC/AC genotypes also implicated an increased risk of PCa (CC+AC vs AA − OR =1.11, 95% CI: 1.05–1.19). The C allele of IGFBP3-202A/C polymorphism was the risk allele for PCa relative to the A allele (OR =1.09, 95% CI: 1.05–1.14). Further stratification analysis revealed that the association between –202A/C polymorphism and PCa risk among Caucasians, but not in other ethnicities, was statistically significant (recessive model, OR =1.10, 95% CI: 1.02–1.19). In addition, the IGFBP3-202A/C polymorphism was associated with PCa risk in both population-based and hospital-based studies in homozygote comparison, recessive model, and allele model.ConclusionOur meta-analysis indicates that the IGFBP3-202A/C polymorphism is associated with the risk of PCa, particularly in Caucasians, with the C allele being the risk allele for PCa.

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Prostate Cancer Risk in Relation to a Single Nucleotide Polymorphism in the Insulin-like Growth Factor-binding Protein-3 (IGFBP3) Gene: a Meta-analysis

Cited by 5 publications

References 39 publications

Reversion of epithelial-mesenchymal transition by a novel agent DZ-50 via IGF binding protein-3 in prostate cancer cells

Reversion of epithelial-mesenchymal transition by a novel agent DZ-50 via IGF binding protein-3 in prostate cancer cells

Association between insulin-like growth factor-binding protein-3 polymorphism -202 A/C and the risk of prostate cancer: a meta-analysis

Polymorphism in <em>IGFBP3</em> gene is associated with prostate cancer risk: an updated meta-analysis

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