| Background Gastric cancer(GC),as a serious global health issue,is the fifth most frequent malignant tumor worldwide,with the fourth highest mortality rate.The occurrence and development of gastric cancer is a mμLti-factor and multi-stage complex process involving the interaction of environmental factors and host factors.Helicobacter pylori(H.pylori)infection is one of the most important environmental factors in the development of gastric cancer,which can not only initiate the Correa cascade reaction to trigger the occurrence of enteric gastric cancer,but also colonize the tumor,epithelium and immune cells for a long time,and even metastase outside the gastric mucosa.Triggering the signaling cascade reaction of various adaptor proteins,leading to the activation of nuclear factors,the production of cytokines and inflammatory factors,and the promotion of malignant biological behaviors such as invasion and metastasis of gastric cancer,epithelial interstitial transformation,and angiogenesis,which not only increase the risk of gastric cancer but also promote the progression of gastric cancer and affect the prognosis,but the pathogenic mechanism is still unclear.In recent years,H.pylori infection has been found to be closely related to Metabolic diseases such as diabetes,hypertension,hyperlipidemics,and Met S.It has also been reported that H.pylori infection can affect glycolysis,amino acid metabolism,fatty acid metabolism,energy metabolism and other metabolic pathways,suggesting that H.pylori infection may affect human metabolic homeostasis.Metabolic remodeling is one of the markers of malignant tumors,which is manifested in enhanced glycolysis,impaired aerobic respiration,up-regulation of amino acids,increased lipid production and enhanced fatty acid βoxidation from the level of metabolomics.It also plays an important role in the occurrence and development of gastric cancer,not only providing energy for the proliferation of cancer cells,but also promoting the acceleration of tumor progression.However,the metabolic changes of cancer cells regulate each other with the microenvironment.As one of the important microbial communities that reside in human body,the regulatory mechanism of H.pylori and gastric cancer metabolism remains unclear.Whether H.pylori infection can affect the metabolic phenotype of gastric cancer and how its mechanism leads to the changes of metabolic phenotype of gastric cancer remain to be explored.PurposeTo investigate the effect and mechanism of H.pylori infection on metabolic phenotype of gastric cancer.MethodsPart I: Effects of Helicobacter pylori infection on metabolic phenotypes of gastric cancer-based on clinical data1.Subjects: This is a cross-sectional study,which reviewed the clinicopathological data of patients with gastric cancer,including 337 cases.The inclusion criteria were: 1)Patients who received gastric cancer surgery in the First Affiliated Hospital of China Medical University from March 2013 to August 2021;2)Histopathological examination confirmed the diagnosis of gastric cancer.Exclusion criteria were as follows: 1)Patients who had received chemotherapy or radiotherapy before biopsy,and patients with secondary recurrence of surgery were excluded;2)Patients with other malignant tumors or a history of malignant tumors;3)Patients with other major chronic diseases,such as stroke,severe heart,liver and kidney insufficiency;4)Patients who had previously been treated with H.pylori eradication.Laboratory and clinical data of patients were extracted from disease records.The study was approved by the Ethics Committee of the First Affiliated Hospital of China Medical University,and all participants signed informed consent.2.Detection of H.pylori infection: Determination of H.pylori infection is determined by using the Helicobacter pylori Ig G antibody detection kit(colloidal gold method),and the instructions of the kit are strictly followed.3.Definition of Met S and determination of related components: Epidemiological data and medical information of each subject were obtained through face-to-face interview or disease records;Height and weight were measured by standardized anthropometry,with average value as the final index.Blood pressure was measured in the supine and seated positions;BMI is calculated as weight(kg)/height(m)2;Venous blood was collected before surgical treatment,and blood glucose,blood lipid(triglyceride,total cholesterol,high density lipoprotein cholesterol,low density lipoprotein cholesterol)and other indicators were measured.Metabolic syndrome was diagnosed according to the criteria of Chinese Diabetes Association.4.Statistical analysis: SPSS v22.0 software was used in this study for statistical analysis.Non-parametric Mann-Whitney U test was used to evaluate the difference between the two groups for data of continuous variables inconsistent with normal distribution,and T-test was used to evaluate the difference between the two groups for data of continuous variables consistent with normal distribution.Chi-square test was used to compare categorical variables.Continuous variables were expressed as mean±SD.Categorical variables are expressed as numbers or percentages.P<0.05 on both sides,the difference was statistically significant.Part II: Effects of Helicobacter pylori infection on metabolic phenotypes of gastric cancer-based on metabonomics1.Subjects: A total of 30 fresh gastric cancer tissue samples were included in this study,which were from patients who received gastric cancer surgery in the First Affiliated Hospital of National Medical University from June 2012 to mid-June 2014.Patients who had received preoperative chemoradiotherapy and those who had previously received H.pylori eradication therapy were excluded.The study was approved by the Ethics Committee of the First Affiliated Hospital of China Medical University and informed consent was signed.The standard strain H.pylori was purchased from ATCC Microbial Strain Preservation Center(ATCC 26695).AGS gastric cancer cell line was purchased from Cell Resource Center,Institute of Basic Medicine,Chinese Academy of Medical Sciences,with STR identification certificate.2.Identification of H.pylori infection: Three methods were used to identify H.pylori infection in gastric cancer tissues,including PCR amplification of H.pylori conserved gene,Warthin-Starry staining,H.pylori Ig G antibody detection,and positive identification of H.pylori infection in gastric cancer tissues by two methods.3.The co-culture model of H.pylori and AGS cells was established.After resuscitation,H.pylori was cultured on BHI plate under the micro-aerobic conditions,with 85%N2,5%O2 and 10%CO2.AGS cells were cultured to logarithmic growth stage using complete medium of RPMI-1640 cells added with fetal bovine serum.The bacterial suspension was prepared,and the AGS cells were infected with H.pylori(MOI=100:1)for 24 h,and the co-culture model was established.4.Metabolite extraction and untargeted metabolomics sequencing: The metabolites of gastric cancer tissues were extracted according to conventional standards and sequenced by Vanvosh ultra-high performance liquid chromatogram-mass spectrometry(UHPLC-MS/MS)system and Orbitrap Q Exactive TM HF mass spectrometer combined with Hypesil Gold column.The data were searched and matched with mz Cloud,mz Vault and Mass List databases to obtain qualitative and relative quantitative results of metabolites.The metabolites of co-cultured gastric cancer cells were extracted according to conventional standards and sequenced by the Vanquish ultra-high performance liquid phase system combined with Thermo Orbitrap Exploris 120 mass spectrometry detector.The metabolites were identified by comparison with HMDB massbank,Lipid Maps and mzcloud.5.Differential metabolite screening,identification and pathway enrichment analysis: VIP> 1;1 and P < 0.05 Differential metabolites were screened and identified.HMDB database was used for metabolite annotation.Metabolic function analysis was performed using the KEGG database based on the Metabo Analyst 5.0 website.Part III: Study on the mechanism of Helicobacter pylori mediating abnormal fatty acid metabolism in gastric cancer cells1.Subjects of study: AGS gastric cancer cell line and HGC27 gastric cancer cell line were purchased from Cell Resource Center,Institute of Basic Medicine,Chinese Academy of Medical Sciences.Both cells had STR identification certificate.The standard strain H.pylori was purchased from ATCC Microbial Strain Preservation Center,No.ATCC 26695.2.The Si RNA interference cell line was constructed,and the bacterial cell co-culture model was constructed by infecting AGS cells with H.pylori(MOI=100:1)for 24 h.3.RNA library construction and transcriptomic sequencing: Trizol method was used to extract total RNA and conduct quality detection.RNA sequencing Library was prepared using KC-Digital TM Stranded m RNA Library Prep Kit for Illumina(?).Finally,the sequencing was performed on Novaseq 6000 sequencer(Illumina)of the PE150 model.The original sequencing data were cleaned after disembarkation,and the differentially expressed genes between groups were identified using the edge R package(P<0.05 and丨 Log2 FC 丨> 1).GO and KEGG enrichment analysis were performed by KOBAS software,P<0.05 was statistically significant.4.Trizol method was used to extract total RNA from cells,and MonScript TMRTIII All-in-One Mix with ds DNase was used to reverse transcription and realtime fluorescence quantitative PCR was used to detect the changes of ACSL5 m RNA expression.5.Extract the cell protein of the experiment and the control group,and use the BCA protein concentration assay kit to detect the protein concentration and quantification,and then Western blot to detect the change of ACSL5 protein expression.6.fatty acyl-CoAs(fatty acyl-CoAs)was extracted,and quantitative analysis was performed by ultra performance liquid chromatography tandem quadrupole mass spectrometry.7.Cell ATP was extracted according to the operation procedure of the enhanced ATP detection kit,and the content of ATP in the experimental group and the control group was detected by chemiluminescence method.8.NADP+ and NADPH were extracted from cells according to the operation procedure of the NADP+/NADPH detection kit,and the ratio of NADP+/NADPH of cells in the experimental group and control group was detected using the enzyme label instrument.9.SPSS v22.0 and Graph Pad Prism v7.0 were used for statistical analysis.T-test was used for normal distribution data and non-parametric test was used for skewed distribution data.P<0.05 was considered statistically significant.Part IV: Effects of ACSL5,a key enzyme in fatty acid metabolism,on biological function of gastric cancer cells and its clinical significance1.Subjects: Tissue samples were collected from 368 patients admitted to the First Affiliated Hospital of China Medical University from December 2012 to December 2019,including 40 cases of non-atrophic gastritis(NAG),84 cases of enteric atrophic gastritis(IM-GA),and 244 cases of gastric cancer(GC).Paracancer IM-GA and distal normal tissue were found in 80 GC cases.The clinicopathologic data of 118 GC patients with complete clinicopathologic parameters were collected.Complete follow-up information was available for 118 GC patients up to June 2022.This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of China Medical University,and each subject signed a written informed consent.Both AGS and HGC27 gastric cancer cell lines were purchased from Cell Resource Center,Institute of Basic Medicine,Chinese Academy of Medical Sciences.Both cell lines had STR identification certificate.2.Construct ACSL5 lentivirus overexpression and Si RNA interference in gastric cancer tool cells.3.Trizol method was used to extract total RNA from cells,and Mon Script TMRTIII All-in-One Mix with ds DNase was used to reverse transcription,and real-time fluorescence quantitative PCR was used to detect the expression of ACSL5 m RNA.4.Extract the cell protein of the experimental group and the control group,and use the BCA protein concentration detection kit to detect the protein concentration and quantitative Western blot to detect the change of ACSL5 protein expression.5.The proliferation ability of cells was detected by CCK-8 assay and Ed U fluorescence staining assay.Scratch healing test,Transwell migration test and Transwell invasion test were used to detect the migration and invasion ability of cells.6.In situ expression of ACSL5 in gastric cancer tissues was detected by immunohistochemical staining.7.SPSS v22.0 and GraphPad Prism v7.0 were used for statistical analysis,and normal distribution data were used t test,and rank sum test was used for biased distribution data.Chisquare test was used to evaluate protein expression and clinicopathological parameters The relationship between.Receiver operating curve(ROC)was used to evaluate the diagnostic value.Survival analysis was performed by log-rank test.P < 0.05 was considered statistically significant.ResultsPart I: Effects of Helicobacter pylori infection on metabolic phenotypes of gastric cancer-based on clinical data1.Difference analysis of metabolism-related parameters in gastric cancer patients with positive and negative H.pylori antibody expressionThe levels of fasting blood glucose(P=0.009),systolic blood pressure(P < 0.001)and diastolic blood pressure(P=0.01)in H.pylori positive group were significantly higher than those in H.pylori negative group.The HDL-C level of H.pylori positive group was significantly lower than that of H.pylori negative group(P=0.007).2.Stratified analysis of metabolic characteristics in patients with gastric cancer with positive and negative H.pylori antibody expressionStratification by sex: In the male group,systolic blood pressure(P < 0.001)and diastolic blood pressure(P=0.005)were significantly increased in the H.pylori positive group,while HDL-C was significantly decreased(P=0.026).H.pylori is mainly associated with blood pressure and lipid metabolism disorders.In the female group,H.pylori positive group significantly increased blood glucose(P=0.023)and significantly decreased HDL-C(P=0.025).H.pylori infection is mainly associated with disorders of blood glucose and lipid metabolism.Stratification by age: In the population over 60 years old,blood glucose(P=0.003),systolic blood pressure(P=0.005)and diastolic blood pressure(P=0.043)were significantly increased in H.pylori positive group.H.pylori is mainly associated with abnormal blood sugar and blood pressure.Among those aged 60 years or less,the infection rate of H.pylori was higher in those with a history of smoking.In the H.pylori positive group,systolic blood pressure(P=0.007)and diastolic blood pressure(P=0.044)were increased,and HDL-C was significantly decreased.The difference in blood lipid was mainly concentrated in the female population(P=0.005).Stratified according to disease progression: In early gastric cancer patients,blood glucose(P=0.019),diastolic blood pressure(P=0.037),TG tended to increase(P=0.078),and HDL-C decreased significantly(P=0.027)in H.pylori positive group.H.pylori is mainly associated with blood sugar,blood pressure and lipid disorders.In patients with advanced gastric cancer,systolic blood pressure(P<0.001)and diastolic blood pressure(P=0.016)were significantly increased in H.pylori positive group.3.Analysis of the difference in the incidence of gastric cancer metabolic syndrome between positive and negative H.pylori antibody expressionA total of 258 patients with complete metabolism-related indexes were included in the analysis.The positive group had increased BMI(P=0.022),dyslipidemia(P=0.011)and blood glucose(P=0.036),and the incidence of hypertension showed an increasing trend(P=0.085).The incidence of metabolic syndrome was significantly higher than that of the negative group(P=0.007).Part II: Effects of Helicobacter pylori infection on metabolic phenotypes of gastric cancer-based on metabonomics1.Effects of H.pylori infection on metabolic phenotypes of gastric cancer tissues(1)Determination of H.pylori infectionBy means of H.pylori conserved gene detection,Warthin-Starry staining and serum Ig G,16 of the 30 fresh gastric cancer samples were positive for H.pylori infection and 14 were negative,with a positive rate of 53.33%.(2)Analysis of different metabolites in gastric cancer tissues with different H.pylori infection status11 metabolites were enriched in H.pylori positive and negative gastric cancer tissues.Cholic acid,cis-2-Decenoic acid,Corchorifatty acid F,gamma-Muurolene,Punicic acid,Adrenolone,p-menthyl-1,3,8-triene were highly enriched in H.pylori-positive gastric cancer tissue.8Z,11 Z,14Z-Eicosanotrienoic acid,Arachidonic acid,Chrysin,L-histidine showed low enrichment in H.pylori positive gastric cancer tissue.(3)Enrichment analysis of different metabolite pathways in gastric cancer tissues with different H.pylori infection statusH.pylori infection is mainly related to unsaturated fatty acid biosynthesis,β-alanine metabolism,Histidine metabolism,arachidonic acid metabolism and other pathways.The unsaturated fatty acid synthesis pathway is the most significant metabolic pathway of H.pylori affecting gastric cancer tissues,and the metabolites involved mainly include8 Z,11Z,14Z-eicosanotrienoic acid and arachidonic acid.2.Effects of H.pylori infection on metabolic phenotype of AGS gastric cancer cells(1)Analysis of different metabolites of AGS gastric cancer cells with different H.pylori infection statusA total of 99 different metabolites were screened between the AGS cells infected with H.pylori and the AGS cells of the control group,among which 52 metabolites were highly enriched in H.pylori positive gastric cancer and 47 were low enriched in H.pylori positive gastric cancer.(2)Enrichment of different metabolite pathways in AGS cells with different H.pylori infection statesH.pylori infection is mainly associated with ABC transporters,central carbon metabolism,purine metabolism,alanine/aspartic acid/glutamate metabolism,pantothenic acid and co A biosynthesis pathways.Differential metabolites can be enriched into the anabolic pathway of unsaturated fatty acids,and the metabolites involved mainly include palmitic acid,linoleic acid,gamlinolenic acid,erucic acid and docosapentenoic acid(22n-3).Part III: Study on the mechanism of Helicobacter pylori mediating abnormal fatty acid metabolism in gastric cancer cells1.Screening and identification of key regulatory molecules of abnormal fatty acid metabolism in gastric cancer cells mediated by H.pylori(1)Effect of H.pylori infection on transcriptomics of AGS cellsCompared with the control group,there were 1473 differentially expressed genes in AGS cells infected with H.pylori,of which 961 m RNA expressions were up-regulated and 512 m RNA expressions were down-regulated.GO and KEGG enrichment analysis of the upper and down-regulated m RNA in AGS cells infected with H.pylori showed that these differential genes were involved in a variety of metabolism-related pathways.(2)Effects of H.pylori infection on fatty acid metabolism pathway and related genes in AGS cellsIn the GO database,three fatty acid-related metabolic pathways were enriched,namely fatty acid metabolism process,long chain fatty acid metabolism process and unsaturated fatty acid metabolism process,involving a total of 18 genes;in the KEGG database,fatty acid anabolism pathway was enriched,involving 3 genes.There were three fatty acid metabolism genes involved in the two databases,which were respectively ACSL5(log2FC2.08,P=6.41E-33),ACSL1(log2FC1.30,P=5.80E-27)and OLAH(log2FC2.57,P=1.49E-09).(3)ACSL5 was the most significant gene affecting fatty acid metabolism in AGS cells infected with H.pyloriNo matter at 6h,12 h and 24 h in co-culture,the m RNA expression of ACSL5 in H.pylori infection group was significantly higher than that of ACSL1 compared with the control group.Therefore,we used ACSL5 as the key regμLatory molecμLe of abnormal fatty acid metabolism of H.pylori mediated gastric cancer cells for follow-up studies.2.H.pylori infection leads to up-regulated expression of ACSL5 in gastric cancer cells(1)H.pylori up-regulated the expression of ACSL5 in gastric cancer cells in a time-dependent mannerH.pylori infected AGS and HGC27 cells with MOI 100:1,and detected the expression of ACSL5 at 6h,12 h and 24 h after infection,respectively.The m RNA and protein levels of ACSL5 began to increase significantly 6 hours after infection,and the gene expression showed a trend of increasing gradually with the extension of infection time.(2)H.pylori up-regulated the expression of ACSL5 in gastric cancer cells in a concentration dependent mannerH.pylori infected AGS and HGC27 cells with different multiple MOI(0,50,100,200).The m RNA and protein expression of ACSL5 increased with the increase of multiple MOI at 6h or 24 h after infection.3.Effects of H.pylori infection up-regulating ACSL5 expression on fatty acid metabolism of gastric cancer cells(1)H.pylori affected the biosynthesis of the long chain fatty acyl-Co As in AGS cellsThe biosynthesis of fatty acyl-CoAs of saturated fatty acids C12:0,C14:0,C16:0,unsaturated fatty acids C18:2,C20:4n6,C20:5n3,C22:6n3 increased significantly in AGS cells of H.pylori infection group.But the fatty acyl-Co As biosynthesis of saturated fatty acids C10:0,C18:0,unsaturated fatty acids C16:1,C18:1 was not significant.H.pylori,as an exogenous stimulus,can promote the synthesis of fatty acyl-Co As,fatty Acyl-Co As.(2)ACSL5 affected the biosynthesis of the long chain acyl-CoAs in AGS cellsfatty acyl-Co As content of unsaturated fatty acids C16:1,C18:1,C18:2,C20:4n6decreased significantly in AGS cells of ACSL5 knockout group.The fatty acyl-Co A content of saturated fatty acid C10:0 increased significantly.ACSL5 can promote the synthesis of fatty acyl-Co As.(3)H.pylori affected the biosynthesis of long-chain fatty acyl-Co As in AGS cells by up-regμLating the expression of ACSL5The contents of C14:0-CoA,C16:0-CoA and C20:4n6-CoA in H.pylori-infected ACSL5 knockout group were significantly decreased compared with the non-treatment group,while the contents of C12:0-Co A were not significantly different between the two groups.H.pylori infection promoted the biosynthesis of C14:0-Co A,C16:0-Co A and C20:4n6-CoA by up-regulating the expression of ACSL5.(4)H.pylori affected the energy metabolism of AGS cells through up-regulation of ACSL5 expressionH.pylori infection increased ATP production in AGS cells without ACSL5 intervention(P=0.012),while ATP production was partially inhibited in AGS cells with ACSL5knockdown(AGS+Hp vs AGS Si301+Hp: P=0.034,AGS+Hp vs AGS Si2183+Hp P=0.023);H.pylori infection increased the NADP+/NADPH ratio of ACSL5 AGS cells(P=0.006).However,the increase of NADP+/NADPH ratio was partially inhibited by H.pylori infection with ACSL5-knocked AGS cells(AGS+Hp vs AGS Si301+Hp:P=0.038,AGS+Hp vs AGS Si2183+Hp P=0.01).This disturbance of energy metabolism may be related to increased catabolism of fatty acids.Part IV: Effects of ACSL5,a key enzyme in fatty acid metabolism,on biological function of gastric cancer cells and its clinical significance1.Effects of ACSL5 on biological function of gastric cancer cells(1)ACSL5 overexpression and knockout tool cell lines were successfully constructedACSL5 overexpression of lentivirus infected AGS and HGC27 cells,the fluorescence efficiency of virus infection 48 h could reach more than 80%.The m RNA and protein expressions of ACSL5 in AGS and HGC27 cells transfected with overexpressed virus were significantly higher than those in no-load control group.The m RNA expression and protein expression of ACSL5 in AGS cells transfected with Si RNA were significantly decreased.(2)ACSL5 promoted the proliferation of gastric cancer cellsThe proliferation of AGS and HGC27 cells overexpressed with ACSL5 was significantly higher than that in the control group.The proliferative ability of AGS cells with ACSL5 knockdown was significantly decreased compared with the no-load control group.Ed U fluorescence staining showed that the proliferation ability of AGS and HGC27 cells overexpressed with ACSL5 was significantly higher than that in no-load control group(P=0.002,P=0.005).ACSL5-knocked AGS cell proliferation ability was significantly decreased compared with no-load control group(Si-301 vs Si-con: P< 0.001;Si-2183 vs.Si-con: P=0.001).(3)ACSL5 promoted the migration and invasion of gastric cancer cellsScratch healing experiment showed that: The percentage of wound healing in AGS and HGC27 cells overexpressed with ACSL5 was significantly higher than that in no-load control group(P<0.001,P=0.009),and the percentage of wound healing in AGS cells knockdown with ACSL5 was significantly lower than that in no-load control group(Si-301 vs Si-con: P< 0.001;Si-2183 vs Si-con: P=0.009).Transwell migration experiment showed that: The number of migrated transmembrane cells in ACSL5 overexpression AGS and HGC27 cells was significantly higher than that in no-load control group(P= 0.006,P< 0.001),and the number of migrated transmembrane cells in ACSL5 knockdown group was significantly lower than that in no-load control group(Si-301 vs.Si-con: P=0.001;Si-2183 vs Si-con: P=0.005).Transwell invasion experiment showed that: The number of transmembrane cells invaded by matrix gel in ACSL5 overexpressed AGS and HGC27 cells was significantly higher than that in no-load control group(P=0.015,P< 0.001),and the number of transmembrane cells invaded by matrix gel in ACSL5 knockdown AGS cells was significantly lower than that in no-load control group(Si-301 vs Si-con: P< 0.001;Si-2183 vs Si-con: P< 0.001).2.Relationship between in situ expression of ACSL5 tissue and risk,clinicopathological parameters and prognosis of gastric cancer(1)m RNA expression characteristics of ACSL5 in gastric cancer tissuesThe GEPIA database was used to compare the m RNA expression level of ACSL5 in 408 cases of STAD and 211 cases of normal gastric tissues.It was found that the m RNA level of ACSL5 in gastric cancer tissues was significantly higher than that in normal gastric tissues.In 30 pairs of gastric cancer and distal normal tissue samples,the expression of ACSL5 in gastric cancer tissue was significantly higher than that in paracancer normal tissue P=0.003),and the average value of paired FC was 2.54 times.(2)The expression characteristics of ACSL5 in gastric cancer and different gastric diseasesACSL5 is expressed in the cytoplasm.The expression of ACSL5 in GC was higher than that of paracancer IM-GA(P < 0.001)and distal normal tissue(P < 0.001).The expression of ACSL5 in different gastric diseases increased gradually in the order of NAG,IM-GA and GC(NAG vs IM-GA,P=0.01;IM-GA vs GC,P< 0.001).(3)The diagnostic value of ACSL5 protein expression in different gastric diseasesWe evaluated the diagnostic value of ACSL5 expression in GC and IM-GA by ROC curve.The resμLts showed that ACSL5 expression had a significant effect on GC(AUC=0.853,P<0.001)and IM-GA(AUC=0.641,P=0.012)had diagnostic value.(4)Correlation between ACSL5 protein expression and clinicopathological parameters of gastric cancerACSL5 protein expression was positively correlated with H.pylori infection(P=0.014).The expression of ACSL5 protein in early gastric cancer was significantly higher than that in advanced gastric cancer(P=0.038),enteric gastric cancer was significantly higher than that in diffuse gastric cancer(P=0.038),middle-highly differentiated gastric cancer was significantly higher than that in poorly differentiated gastric cancer(P=0.022),and the expression of ACSL5 protein in T1 and T2 gastric cancer was higher than that in T3 and T4 gastric cancer(P=0.010).The expression in gastric cancer without peripheral nerve invasion was higher than that in gastric cancer with peripheral nerve invasion(P=0.022).(5)Correlation between ACSL5 protein expression and prognosis of gastric cancerIn our survival analysis of 118 patients with gastric cancer,Kaplan-Meier curve showed no significant difference in overall survival between patients with high and low ACSL5 expression of GC.Conclusion1.H.pylori infection affects the metabolic phenotype of patients with gastric cancer,and is correlated with abnormal blood lipid,blood pressure and blood glucose,and is positively correlated with the increased incidence of metabolic syndrome.2.H.pylori infection affects gastric cancer tissues and cell metabolic phenotypes,and differential metabolites are mainly enriched in fatty acid metabolic pathways.3.H.pylori up-regulates the expression of ACSL5,a key enzyme in fatty acid metabolism,mediates abnormal fatty acid activation and abnormal energy metabolism in gastric cancer cells in a time-and concentration-dependent manner.4.ACSL5,a key enzyme in fatty acid metabolism,can promote the proliferation,migration and invasion of gastric cancer cells.The expression of ACSL5 protein can be used as a diagnostic marker for gastric cancer/atrophic gastritis,which is correlated with H.pylori infection and clinicopathological parameters of gastric cancer,but not prognostic. |
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