Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
Circulating Glypican 4 and mortality risk in patients with metastatic breast cancer-results from the DESIREE study.
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Muendlein Axel, Schmidt Marcus, Brandtner Eva-Maria, Fasching Peter A, van Mackelenbergh Marion, Thill Marc, Heinzle Christine, Bauer Lelia, Link Theresa, Lübbe Kristina, Kümmel Sherko, Hoffmann Oliver, Müller Volkmar, Zahn Mark-Oliver, Denkert Carsten, Müller Lothar, Mundhenke Christoph, Rachakonda Sivaramakrishna, Nekljudova Valentina, Felder Bärbel, Loibl Sibylle, Decker Thomas
Аннотация
BACKGROUND: Glypican 4 (GPC4) is a cell-surface heparan sulfate proteoglycan that can be released into circulation under pathological conditions. This study evaluated the prognostic impact of serum GPC4 levels in patients with metastatic breast cancer.
METHODS: A total of 148 patients from the randomized, placebo-controlled phase II DESIREE trial (HR+/HER2- metastatic breast cancer) were included. Overall survival was the primary endpoint. Serum GPC4 concentrations were measured by enzyme-linked immunosorbent assay.
RESULTS: During a median follow-up of 23 months, 82 patients (55.4%) died. A non-linear, J-shaped association between GPC4 levels and survival was observed. Spline-transformed log2-GPC4 values were significantly associated with mortality (HR 2.72; 95% CI 1.52-4.86; p<0.001). BMI modified this association (p-interaction=0.05), with the strongest association observed in patients with BMI ≥30 (p-interaction=0.014).
CONCLUSION: Circulating GPC4 shows a significant non-linear association with overall survival in HR+/HER2- metastatic breast cancer, with high BMI acting as an important effect modifier.
METHODS: A total of 148 patients from the randomized, placebo-controlled phase II DESIREE trial (HR+/HER2- metastatic breast cancer) were included. Overall survival was the primary endpoint. Serum GPC4 concentrations were measured by enzyme-linked immunosorbent assay.
RESULTS: During a median follow-up of 23 months, 82 patients (55.4%) died. A non-linear, J-shaped association between GPC4 levels and survival was observed. Spline-transformed log2-GPC4 values were significantly associated with mortality (HR 2.72; 95% CI 1.52-4.86; p<0.001). BMI modified this association (p-interaction=0.05), with the strongest association observed in patients with BMI ≥30 (p-interaction=0.014).
CONCLUSION: Circulating GPC4 shows a significant non-linear association with overall survival in HR+/HER2- metastatic breast cancer, with high BMI acting as an important effect modifier.