Prognostic significance of receptor for advanced glycation end products expression in hepatocellular carcinoma after hepatectomy

Ito, Ryusuke; Ishii, Yuji; Wakiyama, Shigeki; Shiba, Hiroaki; Fujioka, Shozo; Misawa, Takeyuki; Ishida, Yuichi; Hano, Hiroshi; Yanaga, Katsuhiko

doi:10.1016/j.jss.2014.06.028

Cited by 9 publications

(3 citation statements)

References 34 publications

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“…We also determined for the first time that RAGE expression is a strong predictor of poor prognosis for GC patients, similar to findings in colorectal cancer, hepatocellular cancer, OSCC and NSCLC [ 9 , 10 , 16 , 17 ]. However, the prognostic impact of RAGE expression appears to differ according to cancer stage ( Fig 4 ).…”

Section: Discussionsupporting

confidence: 67%

Overexpression of the Receptor for Advanced Glycation Endproducts (RAGE) Is Associated with Poor Prognosis in Gastric Cancer

Wang

Shen

et al. 2015

PLoS ONE

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BackgroundThe receptor for advanced glycation endproducts (RAGE) is an oncogenic multidisciplinary trans-membranous receptor, which is overexpressed in multiple human cancers. Recently, it has been shown that RAGE is also involved in carcinogenesis and tumor invasion. In this study, we investigated the expression levels and prognostic value of RAGE in primary gastric cancers (GC).MethodsWe investigated RAGE expression in primary GC and paired normal gastric tissue by real-time quantitative RT-PCR (n = 30) and Western blotting analysis (n = 30). Additionally, we performed immunohistochemistry on 180 paraffin-embedded GC specimens, 69 matched normal specimens.ResultsRAGE was overexpressed in GC compared with the adjacent noncancerous tissues (P＜0.001), and higher RAGE expression significantly correlated with the histological grade (P = 0.002), nodal status(P = 0.025), metastasis status(P = 0.002), and American Joint Committee on Cancer stage (P = 0.020). Furthermore, upregulation of RAGE expression is an independent prognostic factor in multivariate analysis using the Cox regression model (P = 0.001).ConclusionsRAGE Overexpression may be a useful marker to predict GC progression and poor prognosis.

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Section: Discussionsupporting

confidence: 67%

Overexpression of the Receptor for Advanced Glycation Endproducts (RAGE) Is Associated with Poor Prognosis in Gastric Cancer

Wang

Shen

et al. 2015

PLoS ONE

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“…Pusterla et al [65], studying RAGE expression in oval cell from liver by two models: a genetic model of Mdr2−/− RAGE−/− double knockout mice and a pharmacologic blockade of RAGE model, found that RAGE ablation does not affect inflammatory cell recruitment; however the authors identified a novel function of RAGE in regulating oval cell activation and tumor development in inflammation-associated liver carcinogenesis [65]. Confirming these findings, Ito et al [66], studying the expression of RAGE in hepatectomized patients, verified that the higher the expression of these receptors was, the worse the therapeutic outcome of these patients was (lower survival and further development of hepatocellular carcinoma) and, therefore, future therapeutic approaches aimed at the blocking of RAGE need to be tested [66]. …”

Section: Discussionmentioning

confidence: 96%

Choline and Cystine Deficient Diets in Animal Models with Hepatocellular Injury: Evaluation of Oxidative Stress and Expression of RAGE, TNF-α, and IL-1β

Santos

Araújo

Valentim

et al. 2015

Oxidative Medicine and Cellular Longevity

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This study aims to evaluate the effects of diets deficient in choline and/or cystine on hepatocellular injury in animal models (young male Wistar rats, aged 21 days), by monitoring some of the oxidative stress biomarkers and the expression of RAGE, TNF-α, and IL-1β. The animals were divided into 6 groups (n = 10) and submitted to different diets over 30 days: AIN-93 diet (standard, St), AIN-93 choline deficient (CD) diet and AIN-93 choline and cystine deficient (CCD) diet, in the pellet (pl) and powder (pw) diet forms. Independently of the diet form, AIN-93 diet already led to hepatic steatosis and CD/CCD diets provoked hepatic damage. The increase of lipid peroxidation, represented by the evaluation of thiobarbituric acid reactive species, associated with the decrease of levels of antioxidant enzymes, were the parameters with higher significance toward redox profile in this model of hepatic injury. Regarding inflammation, in relation to TNF-α, higher levels were evidenced in CD(pl), while, for IL-1β, no significant alteration was detected. RAGE expression was practically the same in all groups, with exception of CCD(pw) versus CCD(pl). These results together confirm that AIN-93 causes hepatic steatosis and choline and/or cysteine deficiencies produce important hepatic injury associated with oxidative stress and inflammatory profiles.

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“…Studies in growing numbers have reported the concordant over-expression of HMGB1 and RAGE in a variety of cancer types, including hepatocellular carcinoma [ 8 – 11 ]. Several lines of clinical evidence suggested that HMGB1 and RAGE possessed the potentials to serve as powerful prognostic and therapeutic targets for hepatocellular carcinoma [ 12 – 14 ]. The genes coding for HMGB1 and RAGE mapped on different chromosomes carry many polymorphic loci.…”

Section: Introductionmentioning

confidence: 99%

A multicenter matched case-control analysis on seven polymorphisms from HMGB1 and RAGE genes in predicting hepatocellular carcinoma risk

Wang

Liu

et al. 2017

Oncotarget

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Based on 540 hepatocellular carcinoma patients and 540 age- and gender-matched controls, we tested the hypothesis that high mobility group protein box1 (HMGB1) and the receptor for advanced glycation end products (RAGE) genes are two potential candidate susceptibility genes for hepatocellular carcinoma in a multicenter hospital-based case-control analysis. The genotypes of seven widely-studied polymorphisms were determined, and their distributions respected the Hardy-Weinberg equilibrium. The mutant alleles of two polymorphisms, rs1045411 in HMGB1 gene and rs2070600 in RAGE gene, had significantly higher frequencies in patients than in controls (P < 0.001), with the power to detect this significance of being over 99.9%. Moreover, the above two polymorphisms increased the risk of developing hepatocellular carcinoma significantly, particularly for rs2070600 under the additive (odds ratio [OR] = 1.77; 95% confidence interval [CI]: 1.34-2.32; P < 0.001) and dominant (OR = 1.75; 95% CI: 1.23-2.50; P = 0.002) models after adjusting for body mass index, smoking and drinking. Haplotype analysis showed that the T-C-T haplotype (rs1045411-rs2249825-rs1415125) in HMGB1 gene was associated with a 2.47-fold (95% CI: 1.41-4.34; P = 0.002) increased risk of hepatocellular carcinoma compared with the commonest C-C-T haplotype after adjustment. In RAGE gene, the T-T-A-G (rs1800625-rs1800624-rs2070600-rs184003) (adjusted OR; 95% CI; P: 1.75; 1.02-3.03; 0.045) and T-T-A-T (adjusted OR; 95% CI; P: 1.95; 1.01-3.76; 0.048) haplotypes were associated with a marginally increased risk of hepatocellular carcinoma compared with the commonest T-T-G-G haplotype. In summary, we identified two risk-associated polymorphisms (rs1045411 and rs2070600), and more importantly a joint impact of seven polymorphisms from the HMGB1/RAGE axis in susceptibility to hepatocellular carcinoma.

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Prognostic significance of receptor for advanced glycation end products expression in hepatocellular carcinoma after hepatectomy

Cited by 9 publications

References 34 publications

Overexpression of the Receptor for Advanced Glycation Endproducts (RAGE) Is Associated with Poor Prognosis in Gastric Cancer

Overexpression of the Receptor for Advanced Glycation Endproducts (RAGE) Is Associated with Poor Prognosis in Gastric Cancer

Choline and Cystine Deficient Diets in Animal Models with Hepatocellular Injury: Evaluation of Oxidative Stress and Expression of RAGE, TNF-α, and IL-1β

A multicenter matched case-control analysis on seven polymorphisms from HMGB1 and RAGE genes in predicting hepatocellular carcinoma risk

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