Glycosylation gene expression in MM. (A) Selectin ligand biosynthetic pathway. Sialyltransferases, including ST3GAL6, transfer sialic acid from the activated cytidine 5′-monophospho-N-acetylneuraminic acid to terminal positions on sialylated glycolipids (gangliosides) or to the N- or O-linked sugar chains of glycoproteins. ST3GAL6 contributes to the formation of selectin ligands and sialyl Lewis X, a carbohydrate important in cell-cell recognition. (B) GSEA software analyzed glycosylation-related genes in MM patients from the previously published data set GSE6477. Shown is a graphic enrichment of a publicly available MSigDB gene set (TRANSFERASE_ACTIVITY_TRANSFERRING_GLYCOSYL_GROUPS) in MM patients (left, red) compared with healthy controls (blue, right). False discovery rate (FDR) = 0.24 and normalized enrichment score (NES) = 1.14. (C) Heat map demonstrating significantly altered glycosylation gene expression pattern in MM patients vs normal donors (ND) with fold change (FC) >1.5 and P < .05. ST3GAL6 is highlighted in red as one of the most significantly enriched glycosylation genes in MM patients. (D) Analysis of ST3GAL6 expression in the GSE6477 data set showing significantly increasing expression of ST3GAL6 with disease progression. Comparison of ST3GAL6 expression in healthy donors (Normal) to that in patients with MGUS, smoldering MM, newly diagnosed MM and relapsed MM shows increasing expression levels of this gene (P = .049, < .0001, .0031, and .0003, respectively; see Table 1). (E) Kaplan-Meier survival proportions analysis of patient outcome data from the MRC IX trial demonstrating high levels of ST3GAL6 expression associated with inferior OS: low (L) = 48 months, high (H) = 36 months. Log-rank P = .041. N (H) = 129, N (L) = 130.