The Thomsen-Friedenreich Antigen: A Highly Sensitive and Specific Predictor of Microsatellite Instability in Gastric Cancer

Abstract

Microsatellite instability (MSI) is a distinct molecular subtype of gastric cancer. In recent years, the clinical consequences of MSI and the therapeutic opportunities to target this peculiar cancer subtype became evident. However, despite the importance of MSI for the stratification of patients, the time and resources required for diagnosis still present an obstacle. In an attempt to identify a new marker for MSI in gastric cancer, we evaluated the expression of five cancer-associated glycan epitopes in a cohort of 13 MSI and 17 microsatellite stable (MSS) cases. Our analysis revealed a highly significant (p < 0.001) association between the expression of the Thomsen-Friedenreich (TF) antigen and MSI status. Hence, we present here the identification of the first single marker for MSI in gastric cancer, excelling with a specificity of 94% (16/17), sensitivity of 69.2% (9/13), negative predictive value of 80% (16/20), and positive predictive value of 90% (9/10). The TF antigen, detected by simple antibody-based assays, is highly specific for carcinoma being undetectable in gastric healthy and premalignant epithelia. This finding lays the basis for new studies and holds promise in improving the rapid identification of MSI in the clinical setting.

Core 1–derived mucin-type O-glycosylation protects against spontaneous gastritis and gastric cancer

“…Therefore, it is likely the lack of complex O-glycosylation due to core 1 O-glycan loss is affecting events at the mucosal surface (where Muc5AC is expressed). Importantly, both glycan truncation and alterations such as αGlcNAc deficiency are reported in gastric cancer (David et al, 1992; Duarte et al, 2016; Li et al, 2018; Mereiter et al, 2018; Springer, 1984; Werther et al, 1994), highlighting the diverse means by which O-glycans and their alterations contribute to gastric homeostasis and disease.…”

“…Although aberrant glycosylation, including loss of complex O-glycans, occurs in patients with gastric cancer (Fu et al, 2016; Mereiter et al, 2018), its exposure level in human gastritis remains unclear. It was shown that Tn-antigen exposure did not change relative to disease status in a patient cohort, being limited to the supranuclear (Golgi-localized region; Barresi et al, 2001).…”

“…For example, differences in ABO blood group antigen expression of glycoproteins modulate Helicobacter pylori binding to gastric mucosa in humans and mice (Borén et al, 1993; Ilver et al, 1998; Magalhães et al, 2009) and influence bacterial burdens and disease (Heneghan et al, 1998; Lindén et al, 2008). Truncated O-glycans have been associated with gastritis and gastric cancer (Balmaña et al, 2018; Mereiter et al, 2018). Exposure of the immature glycan Tn antigen is observed in biopsies of gastritis and gastric cancer patients independent of H. pylori status (Barresi et al, 2001; Persson et al, 2017).…”

Analysis of the Effect of Increased α2,3-Sialylation on RTK Activation in MKN45 Gastric Cancer Spheroids Treated with Crizotinib

“…Aberrant glycosylation on the cell surface is considered a hallmark of cancer with potential applications in the clinical setting [16]. In this regard, GC has been shown to express simple O-glycan antigens [19], and recently an association between the expression of the glycan antigen Thomsen-Friedenreich (TF) and the MSI status of GC tumors has been described, highlighting this glycan antigen as a biomarker with potential consequences for patient stratification [40].…”

The architecture of the IgG anti-carbohydrate repertoire in primary antibody deficiencies

“…52 For instance, we observed low antibody reactivity to TACAs known to be expressed on CVID-associated malignancies, such as GM1 in non-Hodgkin lymphoma 37 or Thomson-Friedenreich antigen in gastric cancer. 53,54 However, tumor glycosylation patterns and their immunoreactivity remain to be fully explored for CVID-associated malignancies.…”