Expression Of Solute Carrier Organic Anion Transporter Family Member 4a1(SLCO4A1) In Acute Myeloid Leukemia And Its Correlation With Prognosis

ObjectiveAcute myeloid leukemia(AML)is the type with the highest incidence of adult leukemia,and its incidence increases with age.Because of its high heterogeneity and easy recurrence,the average 5-year overall survival rate for adults is approximately 27%.Among adults over the age of 60,the 5-year overall survival rate is less than 10%.Therefore,finding biomarkers for the onset,recurrence and prognosis of AML has great significance for evaluate AML patients’ prognosis and the development of treatment strategies.The purpose of this study is to explore the role of solute carrier organic anion transporter family member 4A1(SLCO4A1)in the occurrence and prognosis assessment of AML,reveal its expression pattern and contained biological functions in disease,and explore its clinical application value.Methods1.Differentially expression of solute carrier organic anion transporter family members in AML were analyzed using the AML related data downloaded from TCGA database and GEO database.The expression levels of SLCO4A1 in AML and normal group were analyzed using those data.Differential expression analysis and univariate Cox analysis were used to find the genes associated with AML occurrence and survival,and SLCO4A1 was found to be up-regulated in AML patients and associated with AML prognosis.In addition,SLCO4A1 expression levels in bone marrow,peripheral blood and FAB classification of AML patients were analyzed.And the potential molecular function of SLCO4A1 were speculated via Weighted gene co-expression network analysis(WGCNA)、Gene Ontology(GO)、Kyoto Encyclopedia of Genes and Genomes(KEGG)and GSEA.2.AML patients were divided into two groups with high expression and low expression according to the median expression of SLCO4A1,and the correlation between SLCO4A1 expression level and clinical characteristics of AML patients was analyzed.Kaplan-meier survival analysis was performed for patients in the high-expression group and low-expression group.At the same time,the clinical indicators that have an impact on survival were selected and combined with SLCO4A1 expression,multivariate Cox regression analysis was conducted to verify whether SLCO4A1 is an independent factor affecting the prognosis of AML.3.Marrow from AML patients and healthy people was collected,and expression levels of SLCO4A1 in these samples were detected by fluorescence real time PCR(qRT-PCR).4.The AML cell lines,HL-60 and U937,were treated with all-trans retinoic acid(ATRA)and the expression levels of SLCO4A1 were then determined by qRT-PCR.Results1.Univariate Cox analysis and differential expression analysis were performed on AML related data in TCGA and GEO data sets,and it was found that SLC04A1 expression was up-regulated in AML samples and correlated with the prognosis of AML.2.Expression levels of SLCO4A1 were significantly up regulated in bone marrow and peripheral blood of AML patients when compared with healthy donors.When compared with leukemia stem,the expression levels of SLCO4A1 were also up-regulated.Besides,the M3 subtype of leukemia had the lowest expression levels of SLCO4A1 among all subtypes of leukemia.3.Survival analysis showed that the overall survival rate of patients with high expression levels of SLCO4A1 was significant lower than those with low expression levels of SLCO4A1.Multivariate cox regression analysis showed that high expression of SLCO4A1 was an independent poor prognostic factor for AML(p<0.05).4.Weighted gene co-expression network analysis(WGCNA)、Gene Ontology(GO)、Kyoto Encyclopedia of Genes and Genomes(KEGG)and GSEA revealed that SLCO4A1 may be involved in Wnt,MAPK and other signaling pathways.5.The results of qRT-PCR showed that expression levels of SLCO4A1 in samples from AML patients were significantly higher than those in healthy donors.6.Results of qRT-PCR showed that expression levels of SLCO4A1 were decreased in HL-60 and U937 cells in response to treatment with all-trans retinoic acid.Conclusions1.Expression levels of SLCO4A1 were up-regulated in AML and may be a poor prognostic factor in AML,providing a potential biomaker for the prognosis of AML.2.SLC04A1 is associated with a variety of clinical characteristics of AML,affects Wnt,MAPK and other signaling pathways,and participates in the blocked differentiation of AML cells.