alpha2,3 sialic acid processing enzymes expression in gastric cancer tissues reveals that ST3Gal3 but not Neu3 are associated with Lauren's classification, angiolymphatic invasion and histological grade

Abstract

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. Despite progress in the last decades, there are still no reliable biomarkers for the diagnosis of and prognosis for GC. Aberrant sialylation is a widespread critical event in the development of GC. Neuraminidases (Neu) and sialyltransferases (STs) regulate the ablation and addition of sialic acid during glycoconjugates biosynthesis, and they are a considerable source of biomarkers in various cancers. This study retrospectively characterized Neu3 and ST3Gal3 expression by immunohistochemistry in 71 paraffin-embedded GC tissue specimens and analyzed the relationship between their expression and the clinicopathological parameters. Neu3 expression was markedly increased in GC tissues compared with non-tumoral tissues (p<0.0001). Intratumoral ST3Gal3 staining was significantly associated with intestinal subtype (p=0.0042) and was negatively associated with angiolymphatic invasion (p=0.0002) and higher histological grade G3 (p=0.0066). Multivariate analysis revealed that ST3Gal3 positivity is able to predict Lauren's classification. No associations were found between Neu3 staining and clinical parameters. The in silico analysis of mRNA expression in GC validation cohorts corroborates the significant ST3Gal3 association with higher histological grade observed in our study. These findings suggest that ST3Gal3 expression may be an indicator for aggressiveness of primary GC.

Sialylation: A Cloak for Tumors to Trick the Immune System in the Microenvironment

“…ST3Gal III, ST3Gal IV, and ST3Gal VI are implicated in the formation of SLe A and SLe X glycans on the cell surface, which act as binding ligands for selectins and are essential for metastasis [ 68 , 69 ]. The high expression of ST3Gal III has a strong positive correlation with poor prognosis in gastric cancer [ 70 ], and ST3Gal IV is the main enzyme for generating ligands of Siglec-7 and -9 [ 71 , 72 ]. ST3Gal VI generates selectin ligands and accumulates in liver and urinary bladder cancers [ 73 , 74 ].…”