Identifying Potential Biomarkers Of Malignant Pulmonary Nodules Through Targeted Free Fatty Acid Profiles Screening Based On Metabonomics

Background:In recent years,with the improvement of human health awareness and the popularity of low-dose computed tomography,the detection rate of pulmonary nodules is getting higher and higher.Among them,the onset of malignant pulmonary nodules is hidden,and there are no special clinical manifestations in the subclinical stage,so it is very important for the early diagnosis of malignant pulmonary nodules.At present,the diagnosis of benign and malignant pulmonary nodules usually depends on invasive pathological diagnosis,which greatly increases the psychological and economic burden of patients,so for clinicians,it is of great significance to seek a convenient,minimally invasive and efficient detection method and apply it to the early differentiation of benign and malignant pulmonary nodules.Metabonomics is a new research method in the field of medicine,which is of great application value for disease diagnosis by analyzing the metabolic changes of small molecular substances and looking for potential disease markers.Objective:This study intends to use metabonomics to study and compare the plasma free fatty acid spectrum of patients with benign and malignant pulmonary nodules,and to explore whether it can be used as a potential biomarker to distinguish malignant pulmonary nodules from benign pulmonary nodules.so as to help clinicians to improve the diagnosis rate of malignant pulmonary nodules.Design and methods:This study included 283 patients with pathologically confirmed pulmonary nodules who were admitted to The Second Affiliated Hospital of Dalian Medical University from June 2019 to August 2020.According to their pathological results,they were divided into malignant pulmonary nodule group and benign pulmonary nodule group.The age,sex and other basic materials of the patients,common tumor markers such as carcinoembryonic antigen(CEA)and neuron specific enolase(NSE),and Cytokeratin-19-fragment(CYFRA21-1),and 31 kinds of free fatty acids such as palmitic acid,palmitic acid,nerve acid,stearic acid,lauric acid,arachidonic acid,behenic acid and linoleic acid were collected retrospectively.SPSS 25.0 statistical software was used to analyze the expression of plasma free fatty acids between the two groups.The differentially expressed fatty acids were analyzed by multivariate Logistic regression analysis,and the area under ROC curve AUC,was calculated to evaluate the diagnostic efficacy of fatty acid levels in malignant pulmonary nodules.Results:1.Compared with benign pulmonary nodule group,the expressions of total fatty acid,total saturated fatty acid,palmitic acid,stearic acid,total W3,22 carbon tetraenoic acid,linolenic acid,22 carbon pentaenoic acid and nerve acid were significantly increased in malignant pulmonary nodule group,the difference was statistically significant.2.Multivariate Logistic regression analysis of differentially expressed fatty acids and common tumor markers CEA,NSE and CYFRA21-1 showed that stearic acid was an independent risk factor for malignant pulmonary nodules.3.By calculating the area under the ROC curve of stearic acid and three commonly used clinical tumor markers(CEA,NSE,CYFRA21-1),it was found that the diagnostic value of stearic acid(AUC=0.643)in malignant pulmonary nodules was higher than that of traditional tumor markers CEA(AUC=0.546),NSE(AUC=0.557)and CYFRA21-1(AUC=0.495),and its specificity was higher than that of the other three tumor markers.Conclusions:1.The expression of total fatty acid,total saturated fatty acid,stearic acid,palmitic acid,total W3,22 carbon tetraenoic acid,linolenic acid,22 carbon pentaenoic acid and nerve acid increased in patients with malignant pulmonary nodules.In addition,stearic acid is an independent risk factor for the occurrence of malignant pulmonary nodules.It is suggested that the expression of plasma free fatty acids may have a certain predictive value for the occurrence of malignant pulmonary nodules.2.Stearic acid has a better ability to distinguish benign pulmonary nodules from malignant pulmonary nodules than common clinical tumor markers,which suggests that stearic acid has the potential to become a biomarker for the diagnosis of malignant pulmonary nodules.