Fucosylated α1-acid glycoprotein as a biomarker to predict prognosis following tumor immunotherapy of patients with lung cancer

Abstract

Immunotherapy targeting immune checkpoint molecules has provided remarkable clinical benefits in cancer patients but no clinically relevant biomarker for predicting treatment outcomes exists. Recently, we demonstrated that glycan structures of serum α1-acid glycoprotein (AGP) changed dramatically in cancer patients and that α1,3fucosylated AGP (fAGP) levels increased along with disease progression and decreased responding to chemotherapy treatments. Here, the fAGP was analyzed in sera prospectively obtained from 39 patients with advanced lung cancer who underwent immunotherapy with anti-PD-1 antibody, nivolumab. Twenty-three patients had significantly high fAGP levels above the cut-off value (H-fAGP) at one month after starting the treatment and 20 patients in this group, whose tumor sizes did not decrease, maintained high fAGP levels continuously and subsequently died. However, the other 16 patients, whose fAGP levels decreased or maintained below the cut-off value (L-fAGP), survived during a 2-year observation even though 5 patients in this group had no tumor shrinkage. Accordingly, the overall survival rate was found to significantly correlate with the fAGP level. Multivariate analyses revealed that the H-fAGP was an independent risk factor for cancer progression. Therefore, the fAGP level appeared to be a reliable biomarker for predicting clinical efficacy of immunotherapy with nivolumab.

Chronic exposure to low doses of ionizing radiation impacts the processing of glycoprotein N-linked glycans in Medaka (Oryzias latipes)

“…A second study, looking at the glycosylation of serotransferrin, reported that biantennary structures containing sialic acid decreased during radiotherapy, and 1 month after finishing the treatment, an abundance of these structures increased, but without reaching the original levels (T oth et al 2016). Glycan related changes that have been identified as markers of inflammation include an increase in the branching of glycan structures in serum proteins (Higai et al 2005) as well as an increase in the levels of sialylation (De Graaf et al 1993;Anthony and Ravetch 2010) and/or fucosylation (Thompson et al 1989;Yokobori et al 2019). Our results, showing an increase in the degree of branching, suggest that inflammation could be a part of the response to chronic exposure to low doses of IR.…”

Multi-Omics Approaches for the Prediction of Clinical Endpoints after Immunotherapy in Non-Small Cell Lung Cancer: A Comprehensive Review

“…Glycan structures can change in association with the presence of a tumor or under certain treatment conditions [ 78 , 79 ]. In a small but prospective cohort treated with nivolumab, fucosylated AGP levels appeared a reliable biomarker [ 80 ].…”

A Sensitive and Reversible Labeling Strategy Enables Global Mapping of the Core‐Fucosylated Glycoproteome on Cell Surfaces

“…FUT8 gene knockout in mice resulted in a high percentage (up to 70–80 %) of early postnatal death due to the major developmental growth and respiratory defects, while the survivors displayed severe growth retardation and emphysema‐like changes in the lungs [2] . Abnormal expression of cell‐surface core fucosylation has been frequently observed in various cancers such as liver, colorectal, ovarian, prostate, and breast cancer, [3] while the high concentration of core fucose often indicated a poor prognosis and decreased survival [4–6] . Studies indicated that core fucosylation promotes tumor growth, invasion, and metastasis through regulating many cell‐surface growth factors such as epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR), and transforming growth factor‐β receptor (TGF‐βR) [7–10] .…”