Epidemiological Factors And Metabolic Biomarkers Of Esophageal Squamous Cell Carcinoma And Precancerous Lesions In Linzhou

Objectives1.To explore the epidemiological influencing factors of esophageal squamous cell carcinoma(ESCC)and its precancerous lesions among Linzhou residents,and to provide theoretical basis for primary prevention of ESCC.2.To identify and validate the metabolic biomarkers for the screening of ESCC and esophageal squamous dysplasia(ESD)subjects,and to provide valuable information for the exploration of biomarkers and the interpretation of metabolic fluctuations in the carcinogenesis of ESCC.3.To assess the combined impact of biomarkers and epidemiological influencing factors on the occurrence of ESCC and precancerous lesions.MethodsFrom October 2018 to October 2019,ESCCs,moderate or severe ESDs and normal controls(NCs)were selected as the subjects of study.Questionnaire survey was carried out to collect the demographic and lifestyle information of the subjects,and collected fasting blood samples for metabolomics testing.The multivariate logistic regression analysis was used to analyze the influencing factors of ESCC and its precancerous lesions.Gas chromatography-mass spectrometry was used to acquire the serum metabolic profiles.Uni-and multivariate analyses were employed to screen and to validate the biomarkers.Pathway analysis was conducted to uncover the fluctuated metabolic pathways during ESCC.The multivariate logistic regression analysis was used to evaluate the combined effect of biomarkers and epidemiological influencing factors on the occurrence of ESCC and precancerous lesions.Results1.Lower level of education,drinking shallow groundwater and well,current smoking,frequent consumption of pickled vegetables and have history of digestive tract diseases were epidemiological influencing factors of ESCC.Lower level of education,smoking,frequent consumption of broccoli and smoked products,have history of digestive tract diseases were epidemiological influencing factors of ESD.2.ESCC,ESD and NC subjects revealed progressively altered metabolic profiles,in which amino acids globally increased while fatty acids decreased in ESCCs compared with control groups.The panel constructed with propanoic acid,linoleic acid,glycerol-3-phosphate and glutamine showed the area under curve(AUC),sensitivity and specificity of 0.812,0.78 and 0.74 in the training set,and of 0.817,0.75 and 0.74 in the validation set,in the discrimination of ESCC/ESD from NC subjects.The combination of propanoic acid,leucine and hydroxyproline revealed satisfactory performance in the discrimination of ESD from NC subjects,the AUC,sensitivity and specificity were 0.803,0.78 and 0.72 in the training set,and were 0.819,0.76 and 0.72 in the validation set.The combination of hypoxanthine,2-ketoisocaproic,glutamate and asparate distinguished ESCC from ESD,the AUC,sensitivity and specificity were 0.826,0.85 and 0.73 in the training set,and were 0.818,0.83 and 0.74 in the validation set.Pathway analysis demonstrated the activated biosynthesis of amino acids and inhibited desaturation of saturated fatty acids.3.High serum levels of glutamine,hypoxanthine and glutamate,lower level of education,drinking shallow groundwater and well,current smoking,frequent consumption of pickled vegetables and have history of digestive tract diseases could increase the risk of ESCC and precancerous lesions,high serum levels of linoleic acid,glycerol-3-phosphate,propanoic acid,leucine,2-ketoisocaproic and frequent consumption of broccoli could reduce the risk of ESCC and precancerous lesions.ConclusionsLifestyle,diet and history of digestive tract diseases can affect the occurrence of ESCC and precancerous lesions in Linzhou.In particular,lower education,smoking and have history of digestive tract diseases are the common risk factors.Due to its geographical characteristics,corresponding preventive measures should be taken according to relevant influencing factors.This study identified novel serum metabolites that highly distinguished ESCC and ESD patients from healthy subjects,which had wide application prospect in the diagnosis of ESCC and ESD.The combination of metabolomic biomarkers and epidemiological influencing factors has important public health significance for the prevention and control of cancer,and provides new ideas for the precise prevention and control of ESCC and ESD.