Metabolomic studies of human gastric cancer: Review

Jayavelu, Naresh Doni

doi:10.3748/wjg.v20.i25.8092

Cited by 61 publications

(49 citation statements)

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“…Given the importance of metabolic cues in the regulation of inflammatory responses both in macrophages as well as T-cells, metabolomics has been used to study such perturbations in numerous diseases (Jayavelu and Bar 2014; Wen et al, 2013; Barallobre-Barreiro et al 2013; Wang et al 2010; DeFeo et al 2011; Lu et al 2013; Noga et al 2012). However, the role of metabolomics in sarcoidosis has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics connects aberrant bioenergetic, transmethylation, and gut microbiota in sarcoidosis

et al. 2016

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Sarcoidosis is a systemic granulomatous disease of unknown etiology. Granulomatous inflammation in sarcoidosis may affect multiple organs, including the lungs, skin, CNS, and the eyes, leading to severe morbidity and mortality. The underlying mechanisms for sustained inflammation in sarcoidosis are unknown. We hypothesized that metabolic changes play a critical role in perpetuation of inflammation in sarcoidosis. 1H nuclear magnetic resonance (NMR)-based untargeted metabolomic analysis was used to identify circulating molecules in serum to discriminate sarcoidosis patients from healthy controls. Principal component analyses (PCA) were performed to identify different metabolic markers and explore the changes of associated biochemical pathways. Using Chenomx 7.6 NMR Suite software, we identified and quantified metabolites responsible for such separation in the PCA models. Quantitative analysis showed that the levels of metabolites, such as 3-hydroxybutyrate, acetoacetate, carnitine, cystine, homocysteine, pyruvate, and trimethylamine N-oxide were significantly increased in sarcoidosis patients. Interestingly, succinate, a major intermediate metabolite involved in the tricyclic acid cycle was significantly decreased in sarcoidosis patients. Application of integrative pathway analyses identified deregulation of butanoate, ketone bodies, citric cycle metabolisms, and transmethylation. This may be used for development of new drugs or nutritional modification.

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Section: Introductionmentioning

confidence: 99%

Metabolomics connects aberrant bioenergetic, transmethylation, and gut microbiota in sarcoidosis

et al. 2016

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“…The development of metabolome analysis tools is allowing the application of comprehensive analyses of energy metabolism pathways such as glycolysis, pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, urea cycle, amino acid and nucleotide metabolisms, and GSH metabolism in cells and tissues. Several articles have been published on metabolomic applications in gastric cancer (27,34,35). However, none have focused on associations between energy metabolism and CD44v9 expression.…”

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confidence: 99%

<b>CD44 variant 9 expression as a predictor for gastric cancer recurrence: immunohistochemical and metabolomic analysis of surgically resected </b><b>tissues </b>

et al. 2017

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CD44 variant 9 (CD44v9) and the heavy chain of 4F2 cell-surface antigen (CD98hc) appear important for regulation of reactive oxygen species defence and tumor growth in gastric cancer. This study examined the roles of CD44v9 and CD98hc as markers of gastric cancer recurrence, and investigated associations with energy metabolism. We applied capillary electrophoresis time-of-flight mass spectrometry to metabolome profiling of gastric cancer specimens from 103 patients who underwent resection with no residual tumor or microscopic residual tumor, and compared metabolite levels to immunohistochemical staining for CD44v9 and CD98hc. Positive expression rates were 40.7% for CD44v9 and 42.7% for CD98hc. Various tumor characteristics were significantly associated with CD44v9 expression. Five-year recurrence-free survival rate was significantly lower for CD44v9-positive tumors (39.1%) than for CD44v9-negative tumors (73.5%; P < 0.0001), but no significant differences in recurrence-free survival were seen according to CD98hc expression. Uniand multivariate analyses identified positive CD44v9 expression as an independent predictor of poorer recurrence-free survival. Metabolome analysis of 110 metabolites found that levels of glutathione disulfide were significantly lower and reduced glutathione (GSH)/ glutathione disulfide (GSSG) ratio was significantly higher in CD44v9-positive tumors than in CD44v9-negative tumors, suggesting that CD44v9 may enhance pentose phosphate pathway flux and maintain GSH levels in cancer cells.Gastric cancer is the fifth most common malignancy (952,000 cases in 2012) and the third leading cause of cancer-related deaths (723,000 deaths in 2012) worldwide (1). Despite the decline in global patient numbers, gastric cancer remains one of the most prevalent cancers in Japan. Although progress in early diagnosis and adjuvant therapy has improved outcomes for gastric cancer patients, radical surgery remains the primary approach for gastric cancer treatment. Outcomes are still unsatisfactory, because gastric cancers relapse with local or distant metastasis even after radical gastrectomy. More specific diagnostic and therapeutic targets are urgently needed to achieve better clinical applications in this field. CD44, a major adhesion molecule for the extracellular matrix, is a single-pass type I transmembrane protein that serves as a cell surface receptor for hyaluronic acid, and has been implicated in vari-

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“…[ ] The mainly pathological features of CAG involved atrophy of gastric mucosa, decrease of gastric acid secretion, activation of gastric parietal cells and intrinsic factors, lack of serum autoantibodies, hypochlorite and vitamin B12, and neurological symptoms and diffuse metaplasia. [ ] In some cases, CAG showed significant spasmolytic polypeptide expressing metaplasia (SPEM) and intestinal metaplasia.2 [ ] Previous studies have shown that the mechanism of CAG is due to oxidative stress, inflammation, and endothelial and mucosal dysfunction. [ ] However, its accurate mechanism is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Urinary metabolomics research for Huangqi Jianzhong Tang against chronic atrophic gastritis rats based on 1H NMR and UPLC-Q/TOF MS

Jin

Qin

Zheng

2020

Journal of Pharmacy and Pharmacology

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Objectives As a traditional Chinese medicine (TCM), Huangqi Jianzhong Tang (HQJZ) has a good efficacy in treating chronic atrophic gastritis (CAG). Our objective was to determine its mechanism based on the urine comprehensive metabolome. Methods In the study, a metabolomic approach was applied to reveal the efficacy of HQJZ on the constructed CAG rats coupled with proton nuclear magnetic resonance (1H NMR) and ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry (UPLC‐Q/TOF MS). Key findings The results showed the regulatory effect of HQJZ on urinary metabolism disorder in CAG rats was similar to the positive drug teprenone. Nineteen and 16 potential biomarkers related to CAG were detected by NMR and UPLC‐Q/TOF MS, respectively. Thirty‐two urine metabolites were significantly regulated by HQJZ treatment. Combined with MetPA and partial least square regression analysis (PLS‐RA), three metabolic pathways of valine, leucine and isoleucine, TCA cycle, and glycine, serine and threonine metabolism were the most relevant pathways for HQJZ treatment. Conclusions The main mechanism of HQJZ might be due to the balance of energy consumption, inflammatory inhibition, improvement of the immune system and oxidative stress on the constructed CAG rats. These findings provided comprehensive metabolic information of TCM by parallel measurements by LC‐MS and NMR.

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Metabolomic studies of human gastric cancer: Review

Cited by 61 publications

References 0 publications

Metabolomics connects aberrant bioenergetic, transmethylation, and gut microbiota in sarcoidosis

Metabolomics connects aberrant bioenergetic, transmethylation, and gut microbiota in sarcoidosis

<b>CD44 variant 9 expression as a predictor for gastric cancer recurrence: immunohistochemical and metabolomic analysis of surgically resected </b><b>tissues </b>

Urinary metabolomics research for Huangqi Jianzhong Tang against chronic atrophic gastritis rats based on 1H NMR and UPLC-Q/TOF MS

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