Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer

Rodrigues, Pedro Luiz Coelho; Maia, L.L.; Santos, Marcelo dos; Peterle, Gabriela Tonini; Alves, L.U.; Takamori, Jean Tetsuo; Souza, Rafael Pereira de; Barbosa, Wagner Miranda; Mercante, A.M.C.; Nunes, Fábio Daumas; Carvalho, Marcos Brasilino de; Tajara, Eloíza H.; Louro, Iúri Drumond; Silva, Adriana Madeira Álvares da

doi:10.4238/2015.november.24.5

Cited by 14 publications

(13 citation statements)

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“…Furthermore, a recent study reported that LEPR demonstrated distinct expression patterns in different histological subtypes of thyroid carcinoma and positive LEPR expression was associated with a longer disease‐free survival in patients with anaplastic thyroid carcinoma . In addition to this evidence and consistent with the findings of the current study, a previous study reported that downregulation of LEPR expression increases the risk of metastasis . Moreover, low LEPR expression was found to be associated with more aggressive tumors .…”

Section: Discussionsupporting

confidence: 90%

“…37 In addition to this evidence and consistent with the findings of the current study, a previous study reported that downregulation of LEPR expression increases the risk of metastasis. 38 Moreover, low LEPR expression was found to be associated with more aggressive tumors. 38,39 Biologically, methylation in the promoter-associated CpG sites of LEPR presumably downregulates LEPR expression in RCC tumors, and this assumption is supported indirectly by the information reported in the TCGA portal regarding LEPR expression in tissue pairs of RCC TU and N-Adj tissues.…”

Section: Original Articlementioning

confidence: 99%

“…38 Moreover, low LEPR expression was found to be associated with more aggressive tumors. 38,39 Biologically, methylation in the promoter-associated CpG sites of LEPR presumably downregulates LEPR expression in RCC tumors, and this assumption is supported indirectly by the information reported in the TCGA portal regarding LEPR expression in tissue pairs of RCC TU and N-Adj tissues. Epigenetic regulation of LEPR expression has been suggested previously in thyroid cancer cells.…”

Section: Original Articlementioning

confidence: 99%

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Prognostic significance of promoter CpG island methylation of obesity‐related genes in patients with nonmetastatic renal cell carcinoma

Mendoza-Pérez

Herrera

et al. 2017

Cancer

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Background Over 40% of renal cell carcinoma (RCC) cases in the US are attributed to excessive body weight. Moreover, obesity may also be linked to RCC prognosis. However, the molecular mechanism underlying these associations are unclear. In the present study, we evaluated the role of promoter methylation in obesity-related genes in RCC tumorigenesis and recurrence. Methods Paired tumors (TU) and normal adjacent (N-Adj) tissues of 240 newly diagnosed and previously untreated Caucasian RCC patients were examined. For the discovery phase, 63 RCC-pairs were analyzed. Additional 177 RCC-pairs were evaluated for validation. Pyrosequencing was used to determine CpG methylation in 20 candidate obesity-related genes. An independent TCGA dataset was also analyzed for functional validation. Association between methylation and recurrence was analyzed using multivariate Cox proportional hazards models and Kaplan-Meier survival analysis. Results Methylation in NPY, LEP and LEPR was significantly higher in TU compared with N-Adj tissues (p<0.0001) in both discovery and validation groups. High methylation in LEPR was associated with increased risk of recurrence (HR=3.15; 95%CI: 1.23–8.07; p=0.02). Patients with high-methylation in LEPR had shorter recurrence-free survival than low-methylation group (Log-Rank p=2.25E-03). Additionally, high LEPR methylation in TU was associated with more advanced features (p≤0.05). Consistent with our findings, lower LEPR expression in TU compared with N-Adj tissues (p=1.00E-03) was found in TCGA data. Conclusions Somatic alterations of promoter methylation in NPY, LEP and LEPR genes are involved in RCC-tumorigenesis. Furthermore, LEPR methylation is associated with RCC recurrence. Future research to elucidate the biology underlying this association is warranted.

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Section: Discussionsupporting

confidence: 90%

Section: Original Articlementioning

confidence: 99%

Section: Original Articlementioning

confidence: 99%

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Prognostic significance of promoter CpG island methylation of obesity‐related genes in patients with nonmetastatic renal cell carcinoma

Mendoza-Pérez

Herrera

et al. 2017

Cancer

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“…In total, 44 independent case–control studies with 35,936 subjects (13,711 cases and 22,225 controls) were included. Among them, 20 were Caucasians [15,16,20–23,34,36,37,39–43,45–48], 14 were Asians [9,11–14,17,24,26,33,44], 1 was African [38], and 9 were mixed populations [18,19,25,35]. Twenty-two case–control studies were designed as hospital-based investigation [9,11–14,17,18,21,22,24,26,33,34,38,44,46,48], seventeen studies were designed as population-based investigation [16,19,25,35–37,40,41,43,45,47], and the source of control in other five studies were unknown [15,20,23,39,42].…”

Section: Resultsmentioning

confidence: 99%

Investigation ofleptin receptorrs1137101 G>A polymorphism with cancer risk: evidence from 35936 subjects

Rong

Tang

Wang³

et al. 2019

Bioscience Reports

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Leptin receptor (LEPR) signaling may be involved in promoting angiogenesis and proliferation, inhibiting apoptosis and playing a vital role in the progression of carcinogenesis. A number of studies have focused on the association of LEPR rs1137101 variants with susceptibility of cancer, however, the observed results were controversial. We searched literature on the relationship of LEPR rs1137101 G>A polymorphism with cancer risk by using PubMed and Embase databases, covering all publications up to 14 October 2018. In total, 44 case–control studies with 35,936 subjects were included. After combining all eligible studies, we identified null relationship between LEPR gene rs1137101 G>A polymorphism and overall cancer risk [A vs. G: odds ratio (OR ) = 0.97, 95% confidence interval (CI ) = 0.89–1.06, P = 0.547; AA vs. GG: OR = 0.93, 95% CI = 0.78–1.13, P = 0.476; AA/GA vs. GG: OR = 0.99, 95% CI = 0.91–1.09, P= 0.890 and AA vs. GA/GG: OR = 0.92, 95% CI = 0.82–1.04, P= 0.198]. However, in a subgroup analysis, there was an increased susceptibility of oral and oropharyngeal cancer in AA vs. GA/GG genetic model (OR, 1.83; 95% CI, 1.01–3.33; P=0.048). Considering the limited participants were included, the findings might be underpowered. Sensitivity analysis identified that any independent study omitted did not materially influence the pooled ORs and CIs. The results of publication bias detection showed that there was no evidence of bias. In summary, this analysis indicates that no significant association of cancer risk was identified to be correlated with rs1137101 G>A variants, even in stratified analyses.

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“…The LEPR Gln223Arg G allele and GG genotype have been reported to be linked with some cancers [22,23]. Additionally, the Gln223Arg polymorphism also gives rise to increased susceptibility to Entamoeba histolytica infections in children [24].…”

Section: Discussionmentioning

confidence: 99%

Leptin Receptor Gene Polymorphism and the Risk of Cardiovascular Disease: A Systemic Review and Meta-Analysis

Sun

2017

IJERPH

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Objective: Few studies have assessed the association between leptin receptor (LEPR) gene polymorphism and the risk of cardiovascular disease (CVD). Of the few epidemiological studies on this topic, the results are still controversial. Methods: PubMed and Embase were screened for studies from their inception to 9 October 2016. The pooled odds ratio (OR) with the corresponding confidence intervals (CI) were used to measure the effect size for studies that reported the association under allelic, homozygous, and dominant models. Pre-specified characteristics were conducted in the subgroup analysis. Heterogeneity between subgroups was evaluated by meta-regression analysis. Results: Seven eligible studies involving 44,133 participants were included in our meta-analysis. Borderline significant association was observed between the LEPR gene polymorphism (rs1137101, rs1137100, rs6700896, and rs8179183) and the increased risk of CVD with considerable heterogeneity under the allelic model, and the overall pooled OR (95% CI) was 1.10 (0.99, 1.22). The LEPR gene variant rs6700896, 109G allele, and 109GG genotype were significantly associated with the increased risk of CVD. Furthermore, stratified group analysis revealed that the association was more pronounced for stroke. Race-differences might also cause the considerable heterogeneity and non-significant association. Conclusions: This is the first systematic review and meta-analysis to investigate the association between LEPR gene variants and CVD risk. Some LEPR gene variants were significantly associated with the increased risk of CVD. However, the present study is limited in its small number of included studies, considerable heterogeneity, and observational study design. Further research is still warranted to confirm the magnitude of the association.

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Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer

Cited by 14 publications

References 28 publications

Prognostic significance of promoter CpG island methylation of obesity‐related genes in patients with nonmetastatic renal cell carcinoma

Prognostic significance of promoter CpG island methylation of obesity‐related genes in patients with nonmetastatic renal cell carcinoma

Investigation ofleptin receptorrs1137101 G>A polymorphism with cancer risk: evidence from 35936 subjects

Leptin Receptor Gene Polymorphism and the Risk of Cardiovascular Disease: A Systemic Review and Meta-Analysis

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Leptin receptor expression and Gln223Arg polymorphism as prognostic markers in oral and oropharyngeal cancer

Cited by 14 publications

References 28 publications

Prognostic significance of promoter CpG island methylation of obesity‐related genes in patients with nonmetastatic renal cell carcinoma

Prognostic significance of promoter CpG island methylation of obesity‐related genes in patients with nonmetastatic renal cell carcinoma

Investigation ofleptin receptorrs1137101 G&gt;A polymorphism with cancer risk: evidence from 35936 subjects

Leptin Receptor Gene Polymorphism and the Risk of Cardiovascular Disease: A Systemic Review and Meta-Analysis

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Investigation ofleptin receptorrs1137101 G>A polymorphism with cancer risk: evidence from 35936 subjects