Plasma-free amino acid profiles are predictors of cancer and diabetes development

Bi, Xinyan; Henry, Christiani Jeyakumar

doi:10.1038/nutd.2016.55

Cited by 95 publications

(68 citation statements)

References 87 publications

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“…This group of patients in a relatively early state of the disease is likely most similar to our group of individuals whom were diagnosed in less than two years after blood sampling and had the lowest histidine levels of all cases. Also in other cancer-related studies, negative correlations between histidine levels and cancer incidence and/or cancer-associated mortality were observed (31)(32)(33). Remarkably, a recent report demonstrated also lower efficacy of cancer treatment in individuals with low histidine levels, and suggested histidine supplementation to enhance the efficacy of methotrexate treatment in leukemia (34).…”

Section: Discussionmentioning

confidence: 83%

Search for early pancreatic cancer blood biomarkers in five European prospective population biobanks using metabolomics

Fest

Vijfhuizen

Goeman

et al. 2019

Preprint

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Background and aim: Most patients with pancreatic cancer present with advanced disease and die within the first year after diagnosis. Predictive biomarkers that signal the presence of pancreatic cancer in an early stage are desperately needed. We aimed to identify new and validate previously found plasma metabolomic biomarkers associated with early stages of pancreatic cancer. Methods:The low incidence rate complicates prospective biomarker studies. Here, we took advantage of the availability of biobanked samples from five large population cohorts (HUNT2, HUNT3, FINRISK, Estonian biobank, Rotterdam Study) and identified prediagnostic blood samples from individuals who were to receive a diagnosis of pancreatic cancer between one month and seventeen years after blood sampling, and compared these with age-and gender-matched controls from the same cohorts. We applied 1 H-NMR-based metabolomics on the Nightingale platform on these samples and applied logistic regression to assess the predictive value of individual metabolite concentrations, with gender, age, body mass index, smoking status, type 2 diabetes mellitus status, fasting status, and cohort as covariates.Results: After quality assessment, we retained 356 cases and 887 controls. We identified two interesting hits, glutamine (p=0.011) and histidine (p=0.012), and obtained Westfall-Young familywise error rate adjusted p-values of 0.43 for both. Stratification in quintiles showed a 1.5x elevated risk for the lowest 20% of glutamine and a 2.2x increased risk for the lowest 20% of histidine.Stratification by time to diagnosis (<2 years, 2-5 years, >5 years) suggested glutamine to be involved in an earlier process, tapering out closer to onset, and histidine in a process closer to the actual onset. Lasso-penalized logistic regression showed a slight improvement of the area under the Receiver Operator Curves when including glutamine and histidine in the model. Finally, our data did not support the earlier identified branched-chain amino acids as potential biomarkers for pancreatic cancer in several American cohorts. Conclusion:While identifying glutamine and histidine as early biomarkers of potential biological interest, our results imply that a study at this scale does not yield metabolomic biomarkers with sufficient predictive value to be clinically useful per se as prognostic biomarkers. acknowledged for their contribution to the analysis presented in the manuscript. Annika Wolin is thanked for her contribution to the FINRISK sample selection. We would like to thank Peter Würtz (Nightingale) for very useful comments on the study. This work was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative.The Nord-Trøndelag Health Study (The HUNT Study) is a collaboration between

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Section: Discussionmentioning

confidence: 83%

Search for early pancreatic cancer blood biomarkers in five European prospective population biobanks using metabolomics

Fest

Vijfhuizen

Goeman

et al. 2019

Preprint

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“…The abnormal metabolism of BCAA and AAA was regarded as one of the symbols of T2DM. An increase in BCAA and AAA could reduce the glucose oxidation in skeletal muscle, thereby inducing insulin resistance and islet cell failure (Bi & Henry, 2017).…”

Section: Discussionmentioning

confidence: 99%

Zanthoxylum alkylamides improve amino acid metabolism in type 2 diabetes mellitus rats

et al. 2020

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To investigate the effect of Zanthoxylum alkylamides (ZA) on amino acid metabolism of type 2 diabetes mellitus (T2DM), the present study was performed with T2DM rats model induced with high fat and sugar fodder combined with low-dose of streptozotocin. ZA were fed to rats at three different doses of 2, 4, and 8 mg/kg for 28 days and metformin was fed to rats at 135 mg/kg as positive control. The results showed that compared with the normal control, the amino acid levels and the expression of related carrier genes were disordered in T2DM rats. Compared with the model, different doses of ZA could significantly resist (p < .05) the decrease in body weight of T2DM rats and improve hyperglycemia, with the best result observed with the high dose (8 mg/kg). Different doses of ZA could ameliorate the levels of 19 kinds of amino acid in the plasma, jejunum, liver, and skeletal muscle of T2DM rats by regulating the expression of related amino acid transporters including LAT1, SNAT2, CAT1, et al. to thereby ameliorating amino acid metabolism disorder in T2DM rats. Practical applications Previous studies showed that Zanthoxylum alkylamides (ZA) could promote the amino acid metabolism in the jejunum of healthy SD rats, improve protein metabolism disorder of type 1 diabetic rats, and also reduce the risk of metabolic syndrome in fat rats model. Herein, we investigated the effect of ZA on amino acid metabolism in type 2 diabetes mellitus (T2DM) rats. The results indicated that ZA could remarkably improve the abnormal expression of amino acid carriers in the jejunum, liver, and skeletal muscle, thereby ameliorating the disorder of amino acid metabolism in the plasma, jejunum, liver, and skeletal muscle of T2DM rats. Therefore, ZA are potential antidiabetic food/medicine product for the T2DM treatment.

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“…The matter is relevant since insulin resistance and hyperinsulinemia, unfortunately intertwined with diabetes type 2, are considered risk factors for cancer, and this risk has been linked to insulin hyper-activation of PI3K/AKT/mTORC1 signaling [ 26 ]. Thus, in a recent report Fontana and al.…”

Section: Nutrition and The Risk Of Cancer: The Puzzling Question Of Imentioning

confidence: 99%

Is the Response of Tumours Dependent on Dietary Input of Some Amino Acids or on the Ratios Among Essential and Non-Essential Amino Acids? All That Glisters is Not Gold

Dioguardi¹,

Flati²,

Corsetti³

et al. 2018

Preprint

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Production of energy is a main task of cancer cells metabolism, since costs of duplicating are enormous. Although energy is derived in cells by dismantling carbon to carbon bonds of any macronutrient, cancer nutritional needs for energetic purposes have been studied primarily as dependent on glycolysis. Since the end of the last century, awareness of dependence of cancer metabolism on amino acids not only for protein syntheses but also for matching energy needs has grown. The roles of specific amino acids, like glutamine, glycine and serine have been explored in different experimental conditions and reviewed. Moreover, there are epidemiological evidences that some amino acids used as supplement for therapeutic reasons (the branched chain ones) may reduce incidence of liver cancer, and some molecular mechanism has been proposed as functional to their protective action. On the contrary, metabolic signature of some pathology connected with increased risk of cancer, like prolonged hyperinsulinemia in insulin resistant patients, is signed by plasma elevated levels of the same branched chain amino acids, posing puzzling questions to clinicians. Most recently, peculiar formulations of amino acids, deeply different if compared to amino acids compositions normally present in foods, have shown the power to master epigenetics slowing growth or driving cancer cells to apoptotic death, while being even beneficial for normal cells and for animals health and life span. In this review, we will analyze and try to disentangle some of the many knots dealing with complexities of amino acids biology and linked to cancer metabolism.

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Plasma-free amino acid profiles are predictors of cancer and diabetes development

Cited by 95 publications

References 87 publications

Search for early pancreatic cancer blood biomarkers in five European prospective population biobanks using metabolomics

Search for early pancreatic cancer blood biomarkers in five European prospective population biobanks using metabolomics

Zanthoxylum alkylamides improve amino acid metabolism in type 2 diabetes mellitus rats

Is the Response of Tumours Dependent on Dietary Input of Some Amino Acids or on the Ratios Among Essential and Non-Essential Amino Acids? All That Glisters is Not Gold

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