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Serum metabolomics analysis for the progression of esophageal squamous cell carcinoma.

ABSTRACT: BACKGROUND: Previous metabolomics studies have found differences in metabolic characteristics between the healthy and ESCC patients. However, few of these studies concerned the whole process of the progression of ESCC. This study aims to explore serum metabolites associated with the progression of ESCC. METHODS: Serum samples from 653 participants (305 normal, 77 esophagitis, 228 LGD, and 43 HGD/ESCC) were examined by ultra-high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS). Principal component analysis (PCA) was first applied to obtain an overview of the clustering trend for the multidimensional data. Fuzzy c-means (FCM) clustering was then used to screen metabolites with a changing tendency in the progression of ESCC. Univariate ordinal logistic regression analysis and multiple ordinal logistic regression analysis were applied to evaluate the association of metabolites with the risk of ESCC progression, and adjusted for age, gender, BMI, tobacco smoking, and alcohol drinking status. RESULTS: After FCM clustering analysis, a total of 38 metabolites exhibiting changing tendency among normal, esophagitis, LGD, and HGD/ESCC patients. Final results showed 15 metabolites associated with the progression of ESCC. Ten metabolites (dopamine, L-histidine, 5-hydroxyindoleacetate, L-tryptophan, 2'-O-methylcytidine, PC (14:0/0:0), PC (O-16:1/0:0), PE (18:0/0:0), PC (16:1/0:0), PC (18:2/0:0)) were associated with decreased risk of developing ESCC. Five metabolites (hypoxanthine, inosine, carnitine (14:1), glycochenodeoxycholate, PC (P-18:0/18:3)) were associated with increased risk of developing ESCC. CONCLUSIONS: These results demonstrated that serum metabolites are associated with the progression of ESCC. These metabolites are capable of potential biomarkers for the risk prediction and early detection of ESCC.

SUBMITTER: Li X

PROVIDER: S-EPMC8100812 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEsophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor diagnosis. Esophageal squamous dysplasia (ESD) is considered as an immediate precancerous lesion of ESCC. Lack of biomarkers for discriminating ESCC and ESD from healthy subjects limits the early diagnosis and treatment of ESCC. Therefore, a serum metabolomic strategy was conducted to identify and validate potential metabolic markers for the screening of ESCC and ESD subjects.MethodsA total of 74 patients with ESCC, 72 patients with ESD, and 75 normal control (NC) subjects were enrolled in this study. Gas chromatography-mass spectrometry was used to acquire serum metabolic profiles. Pathway analysis was conducted to uncover the fluctuated metabolic pathways during ESCC. Multivariate analyses were used to screen and validate the biomarkers.ResultsESCC, ESD, and NC subjects revealed progressively altered metabolic profiles, in which amino acids globally increased, while fatty acids decreased in ESCCs compared with the control groups. Pathway analysis demonstrated the activated biosynthesis of amino acids and inhibited desaturation of saturated fatty acids. The panel constructed with propanoic acid, linoleic acid, glycerol-3-phosphate, and l-glutamine showed the area under the curve (AUC), sensitivity, and specificity of 0.817, 0.75, and 0.74, respectively, in the discrimination of ESCC/ESD patients from NC subjects. The panel constructed by propanoic acid, l-leucine, and hydroxyproline revealed the AUC, sensitivity, and specificity of 0.819, 0.76, and 0.72, respectively, in the discrimination of ESD from NC subjects. The combination of hypoxanthine, 2-ketoisocaproic acid, l-glutamate, and l-aspartate showed the AUC, sensitivity, and specificity of 0.818, 0.83, and 0.74, respectively, in the discrimination of ESCC patients from ESD subjects.ConclusionsOur study revealed the systematic landscape for metabolic alterations in sera of ESD and ESCC patients. The defined metabolite markers showed reasonable performance in the discrimination of ESCC and ESD patients, and may provide helpful reference for clinicians and biologists.

Project description:Background: Esophageal squamous cell carcinoma (ESCC) is one of the most fatal diseases worldwide. Because early diagnosis is difficult, ESCC is mostly diagnosed at an advanced stage, leading to a poor overall prognosis. The purpose of this study was to explore the differences between plasma metabolic profiles in ESCC patients and healthy controls and to establish a diagnostic model of ESCC. Methods: In this study, a cohort of 310 subjects, containing 140 ESCC patients and 170 healthy controls (HC), was recruited. Participants were randomly separated into a training set (80 ESCCs, 80 HCs) and a validation set (60 ESCCs, 90 HCs) and their plasma metabolomics profiles were analyzed by ultra-performance liquid chromatography-tandem quadruple time-of-flight mass spectrometry (UPLC-QTOF/MS) technique. Univariate statistical analysis and multivariate analysis (MVA) methods were used to identify differential metabolites. Finally, the dysregulated pathways associated with ESCC were further explored and the diagnostic performance of the biomarker panel was evaluated. Results: Metabolic analyses identified 34 significant metabolites involved in the metabolism of amino acids, phospholipids, fatty acids, purine, and choline. Farthermore, an effective diagnostic model for ESCC was constructed based on eight metabolites. This panel of biomarkers consisted of hypoxanthine, proline betaine, indoleacrylic acid, inosine, 9-decenoylcarnitine, tetracosahexaenoic acid, LPE (20:4), and LPC (20:5). The model was verified and evaluated in the validation set. The AUC value of the ROC curve was 0.991(95% CI: 0.981-1.000, CI, Confidence interval), with a sensitivity (SE) of 98.8% and a specificity (SP) of 94.9% for the training set and 0.965(95% CI: 0.936-0.993), with a SE of 88.3% and a SP of 88.9% for the validation set. Among them, three biomarkers, indoleacrylic acid, LPC (20:5), and LPE (20:4), exhibited a trend associated with the ESCC progression. Conclusions: Our study identified a novel plasma biomarker panel, which clearly distinguishes ESCC patients and provides insight into the mechanisms of ESCC. This finding may form the basis for the development of a minimally invasive method for ESCC detection.

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Serum metabolomics analysis for the progression of esophageal squamous cell carcinoma.

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