Study On Correlation Between Central Nervous System Infiltration And Dyslipidemia In Acute Myeloid Leukemia And Bioinformatics

Acute Myeloid Leukemia(AML)is a malignant tumor characterized by abnormal proliferation of leukemic cells derived from bone marrow stem cells,which invade the blood and hematopoietic system.Central Nervous System Leukemia(CNSL)is a rare but severe form of extramedullary infiltration of AML,and it is an important prognostic factor in AML patients.Dyslipidemia is a common metabolic disorder caused by genetic factors or unhealthy diet and lifestyle,including elevated levels of total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and triglycerides(TG),as well as decreased levels of high-density lipoprotein cholesterol(HDL-C).Studies have shown that dyslipidemia is associated with the risk of cancer occurrence and progression.Dyslipidemia can increase the risk of primary liver cancer and promote distant metastasis of solid tumors such as breast cancer,colon cancer,and prostate cancer.However,the relationship between serum lipids and CNS infiltration in AML patients has not been studied yet.In this study,a retrospective analysis of clinical data from patients’ electronic medical records was conducted to investigate the relationship between serum lipids and CNS infiltration in AML patients,and to identify potential genes related to AML CNS infiltration using bioinformatics analysis of the TARGET database,with the aim of providing direction for early prevention of AML CNS infiltration.Methods:Electronic medical records of AML patients diagnosed at the Second Affiliated Hospital of Nanchang University from June 7,2006 to July 16,2022 were collected.A total of 806 patients were included in this study after screening,including 37 patients with CNS infiltration and 769 patients without CNS infiltration.Serum lipid levels,including TC,LDL-C,HDL-C,and TG,obtained from the initial lipid profile at the time of AML diagnosis were collected for all patients.The lipid levels were compared between the two groups,and the correlation between lipid abnormalities,other clinical characteristics,and AML CNS infiltration were analyzed.In addition,the raw count data and corresponding clinical information of 308 AML patients(19 with CNS infiltration and 289 without CNS infiltration)were downloaded from the TARGET database(https://ocg.cancer.gov/programs/target)to construct an expression matrix for transcriptome sequencing data.Differential gene expression analysis was performed to identify genes with differential expression between the infiltration and non-infiltration groups.KEGG pathway analysis,GO enrichment analysis,and protein-protein interaction(PPI)network construction were conducted for the differentially expressed genes.The genes affecting the prognosis of AML in the hub gene were regarded as the final key genes.Results:TG,LDL-C,and TC levels were significantly higher in AML patients with CNS infiltration compared to those without CNS infiltration [TG: 1.68(1.22,3.34)vs 1.42(1.04,1.96),p=0.029;LDL-C: 2.40(1.92,3.05)vs 2.07(1.61,2.54),p=0.004;TC: 4.20(3.35,4.97)vs 3.66(3.66,4.18),p<0.001];The incidence of hypercholesterolem-ia and hyper-LDL-C in AML patients with CNS infiltration was higher compared to those without CNS infiltration(16.2% vs 3.6%,p<0.001;10.8% vs 2.7%,p=0.02).;Moreover,patients with hypertriglyceridemia and low HDL-C had higher WBC counts compared to patients with normal TG and HDL-C levels [7.61(3.15,36.16)vs 5.18(2.10,26.30),p=0.01;7.03(2.53,34.84)vs 4.26(1.960,13.51),p<0.001];There was a negative linear correlation between WBC count and HDL-C level(r=-0.191,p<0.001);Univariate and multivariate logistic regression analysis showed that hypercholesterolemia(OR=4.83,95%CI=1.55-14.99,p=0.006),WBC ≥ 50*10^9/L(OR=2.35,95%CI=1.13-4.89,p=0.022),and age ≤ 45 years(OR=2.32,95%CI=1.19-4.68,p=0.014)were independent risk factors for CNS infiltration in AML patients;The incidence of CNS infiltration in patients with 0,1,2,and 3 risk factors were 1.84%,7.21%,9.6%,and 50%,respectively;In the TARGET database,there were 495 differentially expressed genes between AML infiltrated and non-infiltrated groups,including 262 upregulated genes and 233 downregulated genes.;GO enrichment analysis and KEGG pathway analysis showed that these genes were mainly involved in processes such as cell adhesion,regulation of neuron projection development,cellular response to lipid,lipid raft,mesenchymal development,cell morphogenesis,and metal ion transport(p<0.05);Protein-protein interaction(PPI)analysis of the differentially expressed gene using the STRING database and MCODE plugin in Cytoscape identified 9 hub genes based on the ranking of the highest scores,including IL15,NCR2,CCR7,LCK,CSF2,TIGIT,FCGR3 B,KLRK1,and CD2;Based on whether they affect the prognosis of AML,IL15(HR=1.47,95%CI=1.07-2.02,P=0.017)and FCGR3B(HR=1.40,95%CI=1.02-1.91,P=0.038)genes were identified as the final key genes.Conclusion:The blood lipid levels of AML CNS infiltration patients are generally higher than those of AML CNS non-infiltration patients;hypercholesterolemia,WBC≥ 50*10^9/L and age ≤45 years are independent risk factor for AML CNS infiltration;key genes IL15 and FCGR3 B are genes which may affect blood lipid metabolism.