Galectin-1, a novel promising target for outcome prediction and treatment in SCLC - 15/11/22
, Mabel Cedeño c, Anxo Río-Vilariño b, Ignacio Mahillo-Fernández d, Carlos Galeano c, Natalia Baños e, Jesús García-Foncillas b, Manuel Dómine f, ⁎ , Arancha Cebrián b, ⁎ Abstract |
Introduction |
small-cell lung cancer (SCLC) is one of the most lethal malignancies. Its management is complex due to the lack of biomarkers and limited therapies. Galectin-1 (Gal-1) plays a major role in cancer development and progression. The aim of this study is to assess whether Gal-1 has a predictive role in the disease evolution and its therapeutic potential.
Material and Methods |
The expression level of Gal-1 was examined by using a public RNA-sequencing (77 SCLC patients) and in-house immunohistochemistry (IHC) performed on biopsies from 81 patients. Survival curves and Cox regression analysis were used to assess the prognostic potential of Gal-1. In addition, a SCLC-PDX model was carried out and treated with either OTX008, an inhibitor of Gal-1, or vehicle to assess the effects of Gal-1 inhibition on this disease in vivo.
Results |
Galectin-1 gene (LGALS1) expression showed a strong negative correlation with outcome in SCLC patients with advanced disease (p = 0.007). IHC unveiled that overall survival (OS) was significantly lower among extensive-stage SCLC (ES-SCLC) patient group with increased level of Gal-1 and platelet-to-lymphocyte ratio (PLR) (HR=3.07, 95% CI: 1.62, 5.79, p < 0.001). The SCLC-PDX model showed a significant reduction in tumor size (tumor growth inhibition [TGI] index 73%) without side effects.
Discussion |
in this study, high levels of Gal-1 and PLR were associated with poorer OS in SCLC patients, supporting their utility as clinical prognostic biomarkers. Moreover, the in vivo model suggests the inhibition of Gal-1 as a novel potential therapy for this disease with very poor prognosis.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | Gal-1 worsens survival in patients with extensive stage small-cell lung cancer. |
• | Both Gal-1 and PRL increased worsens survival even more. |
• | Gal-1 can be used as a prognostic marker in SCLC patients. |
• | Inhibition of Gal-1 in a PDX model leads to significantly decreased tumor growth. |
• | Targeting Gal-1 may be an effective approach to treat these patients |
Abbreviations : CTCs, ECOG, ES-SCLC, Gal-1, LDH, LS-SCLC, MLR, NLR, NSCLC, OS, PDX, PFS, PLR, SCLC, TGI
Keywords : Small cell lung cancer, Galectin-1, Platelet-to-lymphocyte ratio, Prognosis, Gal-1 inhibitor
Plan
Vol 156
Article 113987- décembre 2022 Retour au numéro
Article précédent
- In FUS[1−359]‐tg mice O,S-dibenzoyl thiamine reduces muscle atrophy, decreases glycogen synthase kinase 3 beta, and normalizes the metabolome
- Fay Probert, Anna Gorlova, Alexei Deikin, Lucien Bettendorff, Ekaterina Veniaminova, Andrey Nedorubov, Kirill D. Chaprov, Tamara A. Ivanova, Daniel C. Anthony, Tatyana Strekalova
- [11C]glyburide PET imaging for quantitative determination of the importance of Organic Anion-Transporting Polypeptide transporter function in the human liver and whole-body
- Solène Marie, Louise Breuil, Zacharias Chalampalakis, Laurent Becquemont, Céline Verstuyft, Anne-Lise Lecoq, Fabien Caillé, Philippe Gervais, Vincent Lebon, Claude Comtat, Michel Bottlaender, Nicolas Tournier
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?