Dataset Information

Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort.

ABSTRACT: Background:Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors. Objective:In this study, we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Design:Within a nested case-control study of 147 incident HCC cases and 147 matched controls, partial least squares (PLS) analysis related 7 modified healthy lifestyle index (HLI) variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132 targeted serum-measured metabolites and a liver function score. The association between the resulting PLS scores and HCC risk was examined in multivariable conditional logistic regression models, where ORs and 95% CIs were computed. Results:The lifestyle component's PLS score was negatively associated with lifetime alcohol, BMI, smoking, and diabetes, and positively associated with physical activity. Its metabolic counterpart was positively related to the metabolites sphingomyelin (SM) (OH) C14:1, C16:1, and C22:2, and negatively related to glutamate, hexoses, and the diacyl-phosphatidylcholine PC aaC32:1. The lifestyle and metabolomics components were inversely associated with HCC risk, with the ORs for a 1-SD increase in scores equal to 0.53 (95% CI: 0.38, 0.74) and 0.28 (0.18, 0.43), and the associated AUCs equal to 0.64 (0.57, 0.70) and 0.74 (0.69, 0.80), respectively. Conclusions:This study identified a metabolic signature reflecting a healthy lifestyle pattern which was inversely associated with HCC risk. The metabolic profile displayed a stronger association with HCC than did the modified HLI derived from questionnaire data. Measuring a specific panel of metabolites may identify strata of the population at higher risk for HCC and can add substantial discrimination compared with questionnaire data. This trial was registered at clinicaltrials.gov as NCT03356535.

SUBMITTER: Assi N

PROVIDER: S-EPMC6862938 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort.

Assi Nada N Gunter Marc J MJ Thomas Duncan C DC Leitzmann Michael M Stepien Magdalena M Chajès Véronique V Philip Thierry T Vineis Paolo P Bamia Christina C Boutron-Ruault Marie-Christine MC Sandanger Torkjel M TM Molinuevo Amaia A Boshuizen Hendriek H Sundkvist Anneli A Kühn Tilman T Travis Ruth R Overvad Kim K Riboli Elio E Scalbert Augustin A Jenab Mazda M Viallon Vivian V Ferrari Pietro P

The American journal of clinical nutrition 20180701 1

<h4>Background</h4>Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors.<h4>Objective</h4>In this study, we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.<h4>Design</h4>Within a nested case-control study of 147 incident HCC cases and 147 matche ...[more]

PMID: 29924298

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Project description:BackgroundDue to the complicated molecular and cellular heterogeneity in hepatocellular carcinoma (HCC), the morbidity and mortality still remains high level in the world. However, the number of novel metabolic biomarkers and prognostic models could be applied to predict the survival of HCC patients is still small. In this study, we constructed a metabolic gene signature by systematically analyzing the data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and International Cancer Genome Consortium (ICGC).MethodsDifferentially expressed genes (DEGs) between tumors and paired non-tumor samples of 50 patients from TCGA dataset were calculated for subsequent analysis. Univariate cox proportional hazard regression and LASSO analysis were performed to construct a gene signature. The Kaplan-Meier analysis, time-dependent receiver operating characteristic (ROC), Univariate and Multivariate Cox regression analysis, stratification analysis were used to assess the prognostic value of the gene signature. Furthermore, the reliability and validity were validated in four types of testing cohorts. Moreover, the diagnostic capability of the gene signature was investigated to further explore the clinical significance. Finally, Go enrichment analysis and Gene Set Enrichment Analysis (GSEA) have been performed to reveal the different biological processes and signaling pathways which were active in high risk or low risk group.ResultsTen prognostic genes were identified and a gene signature were constructed to predict overall survival (OS). The gene signature has demonstrated an excellent ability for predicting survival prognosis. Univariate and Multivariate analysis revealed the gene signature was an independent prognostic factor. Furthermore, stratification analysis indicated the model was a clinically and statistically significant for all subgroups. Moreover, the gene signature demonstrated a high diagnostic capability in differentiating normal tissue and HCC. Finally, several significant biological processes and pathways have been identified to provide new insights into the development of HCC.ConclusionThe study have identified ten metabolic prognostic genes and developed a prognostic gene signature to provide more powerful prognostic information and improve the survival prediction for HCC.

Project description:BackgroundContested evidence suggests that obesity confers no risk to health in people who have a healthy lifestyle, particularly if there are no metabolic complications of obesity. The aim was to examine the association between adherence to lifestyle recommendations and the absence of metabolic complications on the incident or fatal cardiovascular disease and all-cause mortality across different categories of body mass index (BMI).MethodsThis contemporary prospective cohort study included 339,902 adults without cardiovascular disease at baseline, recruited between 2006 and 2010 from the UK Biobank and followed until 2018-2020. The main exposures were four healthy lifestyle behaviours: never smoker, alcohol intake ≤ 112g/ week, 150 min moderate physical activity or 75 min vigorous activity/week, ≥ 5 servings of fruit or vegetables/day, and we assessed these overall and across the BMI groups. Metabolic complications of excess adiposity were hypertension, diabetes and hyperlipidaemia, and we examined whether obesity was associated with increased risk in the absence of these complications. The outcomes were all-cause mortality, death from, and incident cardiovascular disease (CVD).ResultsIndividuals who met four lifestyle recommendations but had excess weight had higher all-cause mortality; for BMI 30-34.9 kg/m2, the hazard ratio (HR) was 1.42 (95% confidence interval 1.20 to 1.68), and for BMI ≥ 35 kg/m2, HR was 2.17 (95% CI 1.71 to 2.76). The risk was lower, but still increased for people with no metabolic complications; for all-cause mortality, BMI 30-34.9 kg/m2 had an HR of 1.09 (95% CI 0.99 to 1.21), and BMI ≥ 35 kg/m2 had an HR of 1.44 (95% CI 1.19 to 1.74) for all-cause mortality. Similar patterns were found for incident and fatal CVD.ConclusionsMeeting healthy lifestyle recommendations, or the absence of metabolic complications of obesity offsets some, but not all, of the risk of subsequent CVD, and premature mortality in people with overweight or obesity. Offering support to achieve and maintain a healthy weight and to adopt healthy behaviours are likely to be important components in effective preventative healthcare.

Dataset Information

Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort.

Publications

Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort.

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