Study On Metabolomics Of Serum Diagnostic Biomarkers Of Oral Squamous Cell Carcinoma

ObjectiveThe study intends to analyze the serum samples of oral squamous cell carcinoma(OSCC)patients and healthy individuals,OSCC patients and Oral erosive lichen planus(OELP)patients based on metabolomics.Moreover,to screen and identify diagnostic biomarkers of OSCC,the metabolic disorders related to OSCC were explored based on metabolomics,which provided a new perspective for early diagnosis of OSCC.Methods72 OSCC patients,70 healthy people and 75 OELP patients were recruited in total from the First Affiliated Hospital of Zhengzhou University.UHPLC-Q-Orbitrap HRMS was used to analyze the serum samples.Combined with multiple statistical analysis methods to screen and identify the differential metabolites of OSCC.Pathway analysis related to OSCC from the metabolic level of differential metabolites was performed.In addition,in order to establish the potential diagnostic panel,we used binary logistic regression analysis and receiver operating characteristic analysis.Results1.The study is to explore new methods for early diagnosis of OSCC based on UHPLC-Q-Orbitrap HRMS analysis.A total of 21 different metabolites were identified,including amino acids:glutamate,taurine,phenylalanine,etc.;lysophosphatidylcholine(LysoPC):LysoPC(16:0),LysoPC(18:1);carnitine:decanoyl carnitine,octanoylcarnitine and acetyl carnitine;organic acids:lactate,taurine,citric acid and 7 other metabolites;and other compounds such as D-chiro-inositol and oleamide.2.Twenty-one endogenous different metabolites were identified as significantly associated with OSCC.Pathway analysis suggested that OSCC associated with amino acid metabolism,including alanine,aspartate and glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,D-glutamine and D-glutamate metabolism,and phenylalanine metabolism;lipid metabolism,including glycolipid metabolism;taurine and hypotaurine metabolism;Arachidonic acid metabolism and primary bile acid biosynthesis.3.Combined with the area under the ROC curve and the VIP value,the diagnostic panel was composed of LysoPC(16:0)(AUC=0.970,95%CI 0.944,0.997,P<0.05),LysoPC(18:1)(AUC=0.950,95%CI 0.911,0.990,P<0.05),taurine(AUC=0.906,95%CI 0.848,0.964,P<0.05)and glutamate(AUC=0.912,95%CI 0.858,0.967,P<0.05).The established diagnostic panel was evaluated by binary logistic regression and ROC analysis.It had an AUC of 0.998,a sensitivity of 96.1%,a specificity of 99.9%,which showed a good performance.4.The study established a method to distinguish between OSCC and OELP based on the UHPLC-Q-Orbitrap HRMS.A total of 20 differential metabolites were identified,including amino acids:glutamate,leucine,phenylalanine,cysteine and acetyl phenylalanine;organic acids:uric acid and cholic acid;carnitine:acetyl carnitine,octanoylcarnitine and decanoyl carnitine;and other lipids,ketones,phenols and other low-molecular compounds.5.The 20 differential metabolites identified by screening the serum samples of OSCC patients and OELP patients were analyzed for metabolic pathways.Amino acid metabolism includes phenylalanine,tyrosine and tryptophan biosynthesis,D-Glutamine and D-glutamate metabolism,phenylalanine metabolism;primary bile acid biosynthesis and arginine biosynthesis are related to OSCC.The biosynthesis of phenylalanine,tyrosine and tryptophan and D-Glutamine and D-glutamate metabolism have important effects on OSCC.6.Combined with AUC and the VIP value,the diagnostic panel was composed of decanoyl carnitine(AUC=0.905,95%CI 0.841,0.968,P<0.05),cysteine(AUC=0.966,95%CI 0.933,0.999,P<0.05)and cholic acid(AUC=0.965,95%CI0.921,0.999,P<0.05).The established diagnostic model was evaluated by binary logistic regression and ROC analysis.The diagnostic model had an AUC of 0.998,a sensitivity of 98.0%,a specificity of 97.9%,and a good diagnostic performance.7.Combined with the analysis of serum metabolites of OSCC,healthy individuals and OSCC,OELP patients,the results showed that taurine,glutamic acid,citric acid and LysoPC(18:1)were significantly different between the two groups(P<0.05).Compared with OELP,the decrease of metabolites in the OSCC group was more obvious.Additionally,the D-glutamine and D-glutamate metabolism,the primary bile acids biosynthesis,the alanine,aspartate and glutamate metabolism,the taurine and hypotaurine metabolism,and arginine biosynthesis may be related to the malignant transformation of OELP.It could be used for potential targets.ConclusionsThe study provided a new idea for the diagnosis of OSCC.The methods of diagnosing OSCC based on metabolic biomarkers are feasible,which lays the foundation of molecular diagnosis for the diagnosis of OSCC.At the same time,metabolic disordered pathways may be related to the occurrence of OSCC.