| Gastric cancer is originating from gastric mucosal epithelium.Its prognosis is closely related to the timing of diagnosis,so early screening is particularly important.Currently,there is no effective serum bio-marker for the diagnosis of gastric cancer.The gastrointestinal tumor markers applied by clinic are a variety of sugar compounds,of which the range of usage is limited.Also,there are no lipid molecules,while previous studies have reported that lipid molecules are recognized as potential biomarkers in most cancers.The application of mass spectrometry imaging in the study of gastric cancer has been a research hotspot for the past 10 years,but previous studies have used gastroscopy biopsy specimens or surgical specimens in advanced gastric cancer,and there is still a lack of research on early gastric cancer,so the application of mass spectrometry in the screening of lipid serum markers of early gastric cancer has great potential.In this study,atmospheric pressure mass spectrometry imaging was performed on the tissues of 6 cases of early gastric cancer.Through multivariate statistical analysis and non-parametric test,26 variables with significant expression changes in early gastric cancer patients were screened out.Among the 12 metabolites with positive spectrum,6 had the same trend in serum.Further ROC diagnostic tests showed that PC(34:3)and PC(32:0)had extremely high diagnostic efficiency.The relative intensity>0.009925 was used as the diagnostic cut-off value,and the sensitivity and specificity of PC(34:3)in the diagnosis of early gastric cancer were 96.67%and 93.33%,respectively.While the sensitivity and specificity of PC(32:0)were 100%when the relative intensity<0.002684 was used as the diagnostic cut-off value for early gastric cancer.Both metabolites had great potential to be tumor diagnostic markers.The ion source of mass spectrometry used in this study is atmospheric pressure,which has the characteristics of simple sample processing,not requiring vacuum environment and rapid detection,making it a promising technical means for routine clinical examination,which also provides practical conditions for the clinical use of the above markers.According to the interpretation of lipid metabolism profile in the tissues of early gastric cancer,it was found that the most significant change in expression was mainly phospholipid.PC(34:1),a metabolite,had a stable up-regulated expression in the cancer areas of early gastric cancer in our study and in that of advanced gastric cancer in previous studies,so this metabolite had the potential to become a tissue marker of gastric cancer.Correlation analysis showed that PC,PG and PI in cancer areas tended to be lower saturated,while PS tended to be higher saturated.This study is the first to study the lipid metabolism of early gastric cancer by mass spectrometry imaging.Several previous studies have reported that tumors occur in the de novo lipid synthesis pathway.Three enzymes related to the de novo lipid synthesis pathway,FASN,SCD1 and CK alpha,are closely related to tumors.A series of studies have reported that they are overexpressed in a variety of tumors and are potential targets for drug therapy.In this study,immunofluorescence staining of FASN,SCD1 and CK alpha was completed based on frozen sections of early gastric cancer.Semi-quantitative statistical results showed that the expression intensity of FASN,SCD1 and CK alpha in tumor glands was significantly higher than that in adjacent normal glands.The results of immunofluorescence were in accordance with the results of mass spectrometry imaging,which showed that the high expression areas of the three enzymes were consistent with the up-regulation areas of fatty acids and phospholipids in the mass spectrometry,suggesting that the up-regulation of fatty acids in early gastric cancer tissues was related to the over-expression of FASN,while the up-regulation of PC was related to the up-regulation of CK alpha.Alteration in de novo lipid synthesis in gastric cancer occurs at the initiation stage. |
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