Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma

Lucarelli, Giuseppe; Galleggiante, Vanessa; Rutigliano, Monica; Sanguedolce, Francesca; Cagiano, Simona; Bufo, Pantaleo; Lastilla, Gaetano; Maiorano, Eugenio; Ribatti, Doménico; Giglio, Andrea; Serino, Grazia; Vavallo, Antonio; Bettocchi, Carlo; Selvaggi, Francesco Paolo; Battaglia, Michele; Ditonno, Pasquale

doi:10.18632/oncotarget.3823

Cited by 172 publications

(132 citation statements)

References 39 publications

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“…Our above immunohistochemical results found that G6PD was aberrantly high expressed in ccRCC than that of their normal counterparts which was similar to other study conclusions which used different cohorts and with distinct analytical approaches 25, 26. Moreover, we also found that G6PD expression in ccRCC was a prognostic molecular and high expression of G6PD predicted worse overall survival in ccRCC patients.…”

Section: Discussionsupporting

confidence: 90%

Overexpression of G6PD Represents a Potential Prognostic Factor in Clear Cell Renal Cell Carcinoma

Zhang¹,

Yi²,

Yang³

et al. 2017

J. Cancer

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Glucose-6-phosphate dehydrogenase (G6PD) participates in glucose metabolism and it acts as the rate-limiting enzyme of the pentose phosphate pathway (PPP). Recently, G6PD dysregulation has been found in a variety of human cancers. Through analyzing published data in The Cancer Genome Atlas (TCGA), our pilot study indicated that G6PD mRNA expression was significantly higher in advanced Fuhrman grade in clear cell renal cell carcinoma (ccRCC). These clues promoted us to further evaluate the expression profile of G6PD and its prognostic impact in patients with ccRCC. In this study, G6PD expression levels were analyzed in 149 human ccRCC and normal tissues using immunohistochemistry. The results showed that compared with that in the normal renal samples, G6PD was found highly expressed in 51.0% of ccRCC (p<0.05). High expression of G6PD was significantly correlated to tumor extent, lymph node metastasis, Fuhrman grade, and TNM stage of ccRCC (all p<0.05). Moreover, positive G6PD expression was associated with poorer overall survival in ccRCC (p<0.001). In Cox regression analyses, high expression of G6PD also could be an independent prognostic factor for overall survival in ccRCC (p=0.007). This study suggests that overexpression of G6PD is associated with advanced disease status and therefore may become an important prognosticator for poor outcomes in ccRCC, as well as a potential therapeutic target for developing effective treatment modalities.

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Section: Discussionsupporting

confidence: 90%

Overexpression of G6PD Represents a Potential Prognostic Factor in Clear Cell Renal Cell Carcinoma

Zhang¹,

Yi²,

Yang³

et al. 2017

J. Cancer

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“…Interestingly, we found a significant increase in the carbohydrate pathway metabolites (glucose 6-phosphate [G6P], and galactose 1-phosphate (Gal1P) and redox markers (glutathione [GSH] and glutathione disulfide [GSSG]), which are consistent with prior metabolic analysis reported on ccRCC tumors (35)(36)(37).…”

Section: L I N I C a L M E D I C I N Esupporting

confidence: 90%

Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI

Zhang¹,

Udayakumar²,

Cai³

et al. 2017

JCI Insight

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“…Tumor cells require large quantities of different energy sources to support their high rate of proliferation with increased energy consumption, which would lead to alterations of key metabolic pathways 15 .…”

Section: Discussionmentioning

confidence: 99%

Global and targeted serum metabolic profiling of colorectal cancer progression

Yin

Sánchez-Espiridión

Lin

et al. 2017

Cancer

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Background Patients with colorectal adenoma polyps (PLP) are at higher risk of developing colorectal cancer (CRC). However, the development of improved and robust biomarkers to enable screening, surveillance and early detection of PLP and CRC continues to be a challenge. The aim of this study was to identify biomarkers of progression to CRC by metabolomic profiling of human serum samples using a multistage approach. Methods Metabolomic profiling was conducted using Metabolon platform for 30 PLP, 30 CRC and 30 control subjects followed by targeted validation of top metabolites in an additional set of 50 CRC, 50 PLP and 50 controls using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Unconditional multivariable logistic regression models adjusted for covariates were used to evaluate association with PLP and CRC risks. Results For the discovery phase, 404 serum metabolites were detected with 50 metabolites showing differential levels between PLP, CRC and controls (P for trend<0.05). Following validation, three top metabolites (xanthine, hypoxanthine and D-mannose) were validated showing lower levels of xanthine and hypoxanthine and higher level of D-mannose in PLP and CRC cases compared to controls. Further exploratory analysis of metabolic pathways revealed key roles for urea cycle and caffeine metabolism associated with PLP and CRC risks. Additionally, joint effect of top metabolites with smoking and significant interaction with BMI were also observed. Analysis of hypoxanthine to xanthine levels as ratio indicated association with CRC progression. Conclusions Our results suggest the potential utility of circulating metabolites as novel biomarkers for early detection of CRC.

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Metabolomic profile of glycolysis and the pentose phosphate pathway identifies the central role of glucose-6-phosphate dehydrogenase in clear cell-renal cell carcinoma

Cited by 172 publications

References 39 publications

Overexpression of G6PD Represents a Potential Prognostic Factor in Clear Cell Renal Cell Carcinoma

Overexpression of G6PD Represents a Potential Prognostic Factor in Clear Cell Renal Cell Carcinoma

Addressing metabolic heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI

Global and targeted serum metabolic profiling of colorectal cancer progression

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