Dataset Information

Identification of Serum Markers of Esophageal Adenocarcinoma by Global and Targeted Metabolic Profiling.

ABSTRACT: We aimed to identify new serum biomarkers of esophageal adenocarcinoma (EAC).We performed metabolomic analyses of serum samples from 2 sets of case-control pairs in the discovery phase, each consisting of 30 patients with histologically confirmed EAC (cases) from the University of Texas MD Anderson Cancer Center and 30 matched subjects without EAC (controls). We identified metabolites whose levels differed significantly between cases and controls and validated those with the greatest difference in an analysis of 321 EAC cases and 331 controls. We generated a metabolite risk score (MRS) for the metabolites.The levels of 64 metabolites differed significantly between EAC cases and controls in the discovery phase. The metabolites with the greatest difference were amino acid L-proline (LP), ketone body 3-hydroxybutyrate (BHBA), and carbohydrate D-mannose (DM); these differences were confirmed in the validation set. Cases had lower mean levels of LP than controls (22.78 ± 6.79 ?g/mL vs 28.24 ± 8.64 ?g/mL; P < .001) and higher levels of BHBA (18.06 ± 17.84 ?g/mL vs 7.73 ± 9.92 ?g/mL; P < .001) and DM (9.87 ± 4.28 ?g/mL vs 6.28 ± 3.61 ?g/mL; P < .001). Levels of DM were significantly higher in patients with late-stage EAC than early-stage EAC (10.61 ± 4.79 ?g/mL vs 8.97 ± 3.36 ?g/mL; P = .005). Higher levels of LP were associated with significant decrease in risk of EAC (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.18-0.38). A significant increase in risk of EAC was associated with higher levels of BHBA (OR, 4.05; 95% CI, 2.84-5.78) and DM (OR, 7.04; 95% CI, 4.79-10.34). Levels of all 3 metabolites associated with EAC risk in a dose response manner; the level of risk conferred by the metabolites increased jointly with smoking status and body mass index. Individuals with high MRS had significant (7.76-fold) increase in risk of EAC vs those with low MRS. Smokers with high MRS had the greatest risk of EAC (OR, 23.40; 95% CI, 10.95-50.00), compared with never smokers with low MRS.On the basis of a case vs control metabolic profile analysis, levels of LP, BHBA, and DM are associated with risk of EAC. These markers might be used as risk and prognostic factors for patients with EAC.

SUBMITTER: Sanchez-Espiridion B

PROVIDER: S-EPMC4596233 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature

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Identification of Serum Markers of Esophageal Adenocarcinoma by Global and Targeted Metabolic Profiling.

Sanchez-Espiridion Beatriz B Liang Dong D Ajani Jaffer A JA Liang Su S Ye Yuanqing Y Hildebrandt Michelle A T MA Gu Jian J Wu Xifeng X

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 20150519 10

<h4>Background & aims</h4>We aimed to identify new serum biomarkers of esophageal adenocarcinoma (EAC).<h4>Methods</h4>We performed metabolomic analyses of serum samples from 2 sets of case-control pairs in the discovery phase, each consisting of 30 patients with histologically confirmed EAC (cases) from the University of Texas MD Anderson Cancer Center and 30 matched subjects without EAC (controls). We identified metabolites whose levels differed significantly between cases and controls and val ...[more]

PMID: 25998788

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Project description:BackgroundLung cancer is the leading cause of cancer-related mortality worldwide. Low-dose CT (LDCT) imaging is now recommended to screen high-risk lung cancer individuals in the USA. LDCT has resulted in increased detection of stage I lung cancer for which the current standard of care is surgery alone. However, approximately 30% of these patients develop recurrence and therefore are in need of further treatment upon diagnosis. This study aims to explore blood-based inflammatory biomarkers to identify patients at high-risk of mortality for which additional treatment modalities can be offered at time of diagnosis.Patients and methodsRecent work on a small panel of circulating cytokines identified elevated levels of IL-6, a pro-inflammatory cytokine, as an indicator of poor survival for lung cancer patients. To reflect the broader role of inflammation in lung cancer, we examined a large panel of 33 inflammatory proteins in the sera of 129 lung cancer patients selected from the National Cancer Institute-Maryland case-control study. To reduce heterogeneity, we specifically focused our study on stage I lung adenocarcinoma patients.ResultsWe replicated the previous observations that IL-6 is associated with prognosis of lung cancer and extended its utility to prognosis in this highly-selected population of stage I lung adenocarcinoma patients. In addition, we developed a multi-marker, combined prognostic classifier that includes the pro-inflammatory Th-17 cell effector cytokine, IL-17. Patients with high levels of IL-6 and IL-17A had a significantly adverse survival compared with patients with low levels (P for trend <0.0001). Patients in the high risk group, with high levels of both proteins had a 5-year survival rate of 46% in comparison to 93% for those with low levels of both markers. Furthermore, we validated the same trends for the IL-6 and IL-17A prognostic signature in an independent data set.ConclusionsThe results identified here justify further investigation of this novel, combined cytokine prognostic classifier for the identification of high-risk stage I lung adenocarcinoma patients. This classifier has the much-needed potential to identify patients at high risk of recurrence and thus prospectively identify the subset of patients requiring more aggressive treatment regimens at the time of diagnosis.

Dataset Information

Identification of Serum Markers of Esophageal Adenocarcinoma by Global and Targeted Metabolic Profiling.

Publications

Identification of Serum Markers of Esophageal Adenocarcinoma by Global and Targeted Metabolic Profiling.

Similar Datasets

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