期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 156, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113987
关键词
Small cell lung cancer; Galectin-1; Platelet -to -lymphocyte ratio; Prognosis; Gal-1 inhibitor
资金
- Animal Model Core Facility of IIS-Fundacion Jimenez Diaz [ES28079000089]
This study found that high levels of Gal-1 and PLR were associated with poorer prognosis in SCLC patients, supporting their utility as clinical prognostic biomarkers. Additionally, an in vivo model suggested that inhibition of Gal-1 may be a novel potential therapy for this disease with very poor prognosis.
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 in-hibition on this disease in vivo.Results: Galectin-1 gene (LGALS1) expression showed a strong negative correlation with outcome in SCLC pa-tients 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, sup-porting 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.
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