Extracellular <scp>LGALS3BP</scp>: a potential disease marker and actionable target for antibody–drug conjugate therapy in glioblastoma

Dufrusine, Beatrice; Capone, Emily; Ponziani, Sara; Lattanzio, Rossano; Lanuti, Paola; Giansanti, Francesco; Laurenzi, Vincenzo De; Iacobelli, Stéfano; Ippoliti, Roberto; Mangiola, Annunziato; Trevisi, Gianluca; Sala, Gianluca

doi:10.1002/1878-0261.13453

Cited by 20 publications

(15 citation statements)

References 59 publications

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“…Similar to CYFIP2, whether its expression is favourable or adverse appears to be cancer-dependent, but the majority of research suggests that high expression is associated with unfavourable clinical outcomes [ 38 ]. In cancer, the majority of research has focussed on the secreted versions of LGLAS3BP, with LGALS3BP found in plasma, a proposed biomarker for early detection and overall survival in glioma patients [ 39 , 40 ]. Tissue expression has also been investigated and, as in this study, has been shown to be associated with decreased overall survival [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

CA9, CYFIP2 and LGALS3BP—A Novel Biomarker Panel to Aid Prognostication in Glioma

Hudson,

Cho,

Colvin

et al. 2024

Cancers

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Brain cancer is a devastating and life-changing disease. Biomarkers are becoming increasingly important in addressing clinical issues, including in monitoring tumour progression and assessing survival and treatment response. The goal of this study was to identify prognostic biomarkers associated with glioma progression. Discovery proteomic analysis was performed on a small cohort of astrocytomas that were diagnosed as low-grade and recurred at a higher grade. Six proteins were chosen to be validated further in a larger cohort. Three proteins, CA9, CYFIP2, and LGALS3BP, were found to be associated with glioma progression and, in univariate analysis, could be used as prognostic markers. However, according to the results of multivariate analysis, these did not remain significant. These three proteins were then combined into a three-protein panel. This panel had a specificity and sensitivity of 0.7459 for distinguishing between long and short survival. In silico data confirmed the prognostic significance of this panel.

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Section: Discussionmentioning

confidence: 99%

CA9, CYFIP2 and LGALS3BP—A Novel Biomarker Panel to Aid Prognostication in Glioma

Hudson,

Cho,

Colvin

et al. 2024

Cancers

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“…However, the investigations of HSP20 in glioma research is rare. LGALS3BP, namely galectin-3-binding protein, is a glycosylated protein overexpressed in various human tumors and is a potential novel diagnostic biomarker and therapeutic target in GBM deserving further validation [20] . UST encodes uronyl 2-sulfotransferase which transfers sulfate to the 2-position of uronyl residue.…”

Section: Discussionmentioning

confidence: 99%

Neddylation-related gene signature predicts the prognosis and is associated with immune infiltration of glioma

Jiang,

Yin,

Tang

et al. 2024

Preprint

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Background Glioma is the most prevalent malignant tumor that originates from central nervous system. Neddylation, a post-translational modification similar to ubiquitination, is involved in tumorigenesis and progression. However, there were limited studies focused on the neddylation in glioma. Therefore, we aimed to explore the potential role of neddylation in glioma. Methods In this study, neddylation-related genes (NRGs) were identified and were used to construct a prognostic signature for glioma patients. Based on this prognostic index, we also explored the differences in clinical features, mutational landscape, immune cell infiltration between high-risk and low-risk groups. Next, single-cell RNA sequencing analysis was further performed to verify the expression of these genes in NRG signature. At last, one gene selected from the NRG signature were validated by in vitro experiments. Results Seven genes (TOP2A, F2R, UST, HSPA1B, LGALS3BP, UROS, and OSBPL11) were identified to construct the NRG signature, which was able to successfully classify glioma patients into high-risk and low-risk groups. A nomogram based on the NRG signature and other prognostic factors were developed to accurately predict the prognosis of glioma. Significant differences in prognosis, mutational landscape, immune cell infiltration were found between distinct groups. Moreover, in vitro experiments illustrated that knockdown of HSPA1B could inhibit the proliferation, migration, and invasion of glioma cells and also inhibit the polarization of M2 macrophages. Conclusion These findings provide new insights into understanding the relationship between NRGs and glioma development and identify novel biomarkers may help to guiding precise treatments to glioma.

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“…It is a multi-function glycosylated protein, an abundant component of cancer‐derived EVs, and a key regulator of cancer-stroma interactions (reviewed in Capone et al, 2021). It has been described as a biomarker and as a therapeutic target (Dufrusine et al, 2023). Overall, it is a substantially more abundant protein than the Sulf-2 enzyme.…”

Section: Discussionmentioning

confidence: 99%

Galectin-3-binding protein inhibits extracellular heparan 6-O-endosulfatse Sulf-2

Panigrahi,

Benicky,

Aljuhani

et al. 2023

Preprint

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Human extracellular 6-O-endosulfatases Sulf-1 and Sulf-2 are the only enzymes that post-synthetically alter the 6-Osulfation of heparan sulfate proteoglycans (HSPG), which regulates interactions of HSPG with many proteins. Oncogenicity of Sulf-2 in different cancers has been documented and we have shown that Sulf-2 is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC). In spite of its importance, limited information is available on direct protein-protein interactions of the Sulf-2 protein in the tumor microenvironment. In this study, we used monoclonal antibody (mAb) affinity purification and mass spectrometry to identify galectin-3-binding protein (LG3BP) as a highly specific binding partner of Sulf-2 in the secretome of HNSCC cell lines. We validated their direct interactionin vitrousing recombinant proteins and have shown that the chondroitin sulfate (CS) covalently bound to the Sulf-2 influences the binding to LG3BP. We confirmed importance of the CS chain for the interaction by generating a mutant Sulf-2 protein that lacks the CS. Importantly, we have shown that the LG3BP inhibits Sulf-2 activityin vitroin a concentration dependent manner. As a consequence, the addition of LG3BP to a spheroid cell culture inhibited invasion of the HNSCC cells into Matrigel. Thus, Sulf-2 interaction with LG3BP has functional relevance, and may regulate physiological activity of the Sulf-2 enzyme as well as its activity in the tumor microenvironment.

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Extracellular LGALS3BP: a potential disease marker and actionable target for antibody–drug conjugate therapy in glioblastoma

Cited by 20 publications

References 59 publications

CA9, CYFIP2 and LGALS3BP—A Novel Biomarker Panel to Aid Prognostication in Glioma

CA9, CYFIP2 and LGALS3BP—A Novel Biomarker Panel to Aid Prognostication in Glioma

Neddylation-related gene signature predicts the prognosis and is associated with immune infiltration of glioma

Galectin-3-binding protein inhibits extracellular heparan 6-O-endosulfatse Sulf-2

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