Anti-FUT4 monoclonal antibody, clone CSB-5G2

PurposeAs an important glycosyltransferase, fucosyltransferase IV (FUT4) is abnormally upregulated in different types of cancers, but its clinical role remains inexplicit. This work aimed to determine the predictive ability of FUT4 in lung adenocarcinoma (LUAD) after curative resection, as well as to explore the role of a possible FUT4 molecular mechanism on LUAD malignant behavior.MethodsA total of 273 LUAD patients after curative resection with complete clinicopathological and RNAseq data from The Cancer Genome Atlas (TCGA) cohort were collected. Correlation of FUT4 with overall survival (OS) was analyzed based on TCGA and further validated by online Kaplan-Meier Plotter database and IHC in 70 LUAD patients recruited in the First Hospital of China Medical University cohort. Multivariate Cox regression analysis and 1000 bootstrapping were performed to verify the predictive value of FUT4. Gene set enrichment assay (GSEA) was performed to investigate the biological characteristics. Correlation between PD-1 and FUT4 was analyzed based on TCGA cohort and validated by IHC on cohort from our hospital.ResultsIncreased FUT4 expression led to reduced overall survival (OS) of LUAD patients based on TCGA (p=0.006 and 0.001 for dichotomous and trichotomous modeling, respectively) and externally validated in KMPLOTTER (p=0.01) and by IHC based on cohort from our hospital (p=0.005 and p=0.019 for dichotomous and trichotomous modeling, respectively). FUT4 overexpression was an independent high risk factor for OSalong with advancedpT stage and pTNM stage (p=0.001, p=0.037, and p<0.001, respectively). GSEA revealed that FUT4 overexpression might correlate with shortened survival of LUAD patients by promoting cell proliferation via ERBB signaling, and suppressing immune response-related pathways. FUT4 expression positively correlated with PD-1 in TCGA (p=0.026) and validated by IHC on cohort from our hospital (p=0.029).ConclusionsIncreased FUT4 expression led to reduced OS in operable LUAD. FUT4 showed significant correlation with immune response and PD-1 expression.

The initial steps of leukocyte adhesion depend on selectin/ligand interactions. Surface ligands on leukocytes are often modified by addition of the sialyl Lewis x (CD15s) determinant. Biosynthesis of CD15s is dependent upon alpha(2,3)sialyltransferases and alpha(1,3)fucosyl-transferases. We report the isolation of an HL60 cell line variant, HL60A2, that no longer expresses CD15s. HL60A2 cells do not adhere to cytokine-stimulated endothelial cells. Enzymatic assays reveal that this cell line has normal alpha(2,3)sialyltransferase activity but is deficient in the alpha(1,3)fucosyltransferase responsible for biosynthesis of CD15s (FUT7). The fucosyltransferase that constructs the non-sialylated antigen, Lewis x (CD15), is expressed at high levels (FUT4). Transcript analyses show that FUT7 and FUT4 are inversely expressed in HL60 and variant cell lines. HL60A2 cells provide a tool to study the regulation of selectin ligands and corresponding human fucosyltransferase genes.