High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

Background: Leucine-rich α-2 glycoprotein 1 (LRG-1) is a secreted glycoprotein that is mainly produced in the liver. Elevated levels of LRG-1 are found in a multitude of pathological conditions including eye diseases, diabetes, infections, autoimmune diseases, and cancer. In patients with early breast cancer (BC), high intratumoral LRG-1 protein expression levels are associated with reduced survival. In this study, we assessed serum levels of LRG-1 in patients with early BC and investigated its correlation with the presence of disseminated tumor cells (DTCs) in the bone marrow and survival outcomes. Methods: Serum LRG-1 levels of 509 BC patients were determined using ELISA and DTCs were assessed by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. We stratified LRG-1 levels according to selected clinical parameters. Using the log-rank (Mantel–Cox) test and multivariate Cox regression analysis, Kaplan–Meier survival curves and prognostic relevance were assessed. Results: Mean serum levels of LRG-1 were 29.70 ± 8.67 µg/ml. Age was positively correlated with LRG-1 expression (r = 0.19; p < 0.0001) and significantly higher LRG-1 levels were found in patients over 60 years compared to younger ones (30.49 ± 8.63 µg/ml vs. 28.85 ± 8.63 µg/ml; p = 0.011) and in postmenopausal patients compared to premenopausal patients (30.15 ± 8.34 µg/ml vs. 26.936.94 µg/ml; p = 0.002). Patients with no DTCs showed significantly elevated LRG-1 levels compared to the DTC-positive group (30.51 ± 8.69 µg/ml vs. 28.51 ± 8.54 µg/ml; p = 0.004). Overall and BC-specific survival was significantly lower in patients with high serum LRG-1 levels (above a cut-off of 33.63 µg/ml) compared to patients with lower LRG-1 levels during a mean follow-up of 8.5 years (24.8% vs. 11.1% BC-specific death; p = 0.0003; odds ratio 2.63, 95%CI: 1.56—4.36). Multivariate analyses revealed that LRG-1 is an independent prognostic marker for BC-specific survival (p = 0.001; hazard ratio 2.61). Conclusions: This study highlights the potential of LRG-1 as an independent prognostic biomarker in patients with early BC.

Details

OriginalspracheEnglisch
Seiten (von - bis)2789-2798
Seitenumfang10
FachzeitschriftArchives of gynecology and obstetrics
Jahrgang309
Ausgabenummer6
PublikationsstatusVeröffentlicht - Juni 2024
Peer-Review-StatusJa

Externe IDs

Mendeley cbec2478-a5bd-3142-8bf1-3e271af56bf4
ORCID /0000-0002-8691-8423/work/157767440
PubMed 38413424

Schlagworte

Ziele für nachhaltige Entwicklung

ASJC Scopus Sachgebiete

Schlagwörter

  • LRG-1; Early breast cancer; Prognostic marker; Serum marker; Minimal residual disease; Disseminated tumor cells, Breast Neoplasms/blood, Prognosis, Humans, Middle Aged, Biomarkers, Tumor/blood, Kaplan-Meier Estimate, Proportional Hazards Models, Glycoproteins/blood, Aged, 80 and over, Female, Adult, Aged