Portal de investigación
Biomarkers of prognosis and pazopanib response in soft tissue sarcoma: An exploratory analysis.
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Mondaza-Hernandez JL
- Amian-Ruiz R
- Antonio Cordero Varela J
- Carrera-Haro MA
- Rodriguez MC
- Lopez-Alvarez M
- Villar VH
- Ramos R
- Valverde C
- Cruz J
- Martinez-Trufero J
- Hindi N
- Fernandez-Serra A
- Lopez-Guerrero JA
- Moura DS
- Martin-Broto J
Grupos
Abstract
BACKGROUND: Advanced soft tissue sarcoma (STS) is a group of rare and heterogeneous malignancies, requiring better therapeutic strategies. Pazopanib, a widely used second-line treatment, has been suggested to exert immunomodulatory effects, which may be relevant for enhancing response. Specifically, pazopanib reduces immunosuppressive cells like myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) while enhancing the function of dendritic cells, T cells, and NK effectors. Based on this knowledge, we hypothesized that proteins involved in immunomodulation could serve as predictive biomarkers of response to pazopanib. OBJECTIVES: To explore immune-related biomarkers of prognosis and pazopanib response in advanced soft tissue sarcoma using paired pre- and post-treatment tumour samples and complementary preclinical models. DESIGN: Exploratory translational study integrating differential gene expression profiling of clinical specimens with in silico prognostic evaluation and in vitro functional assays in soft tissue sarcoma cell lines treated with pazopanib. METHODS: HTG transcriptome-direct profiling was performed on paired FFPE tumour samples from pazopanib-treated patients, followed by bioinformatic identification of differentially expressed genes and survival correlations, and subsequent validation of candidate biomarkers, at RNA and protein levels in sarcoma cell lines exposed to pazopanib. RESULTS: Using HTG transcriptomics, we identified 38 differentially expressed genes in post-pazopanib STS samples. Among them, SERPINE1 was the most consistent dynamic biomarker, showing a 4.19-fold increase (FDR = 0.016) and correlating with poor survival (progression-free survival (PFS), p = 0.033; disease-free survival (DFS), p = 0.004). In vitro, SERPINE1 upregulation was observed in STS cell lines CP0024 (24h, 1.47-fold; 48h, 1.71-fold), ICP059 (48h, 1.15-fold), and 93T449 (72h, 2.29-fold), with earlier expression in more sensitive cell lines. Protein validation confirmed these results after 48h of treatment. CONCLUSIONS: Our results support SERPINE1 as a biomarker for poor prognosis and suggest its role as an exploratory, hypothesis-generating candidate marker for pazopanib response, warranting further validation in larger cohorts.
© The Author(s) 2026.
Datos de la publicación
- ISSN/ISSNe:
- 1758-8340, 1758-8359
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 42542734
- Factor de Impacto:
- 1,488 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
Therapeutic Advances in Medical Oncology SAGE PUBLICATIONS LTD
Citas Recibidas en Web of Science: 1
Documentos
Filiaciones
Keywords
- biomarkers; pazopanib; preclinical; sarcoma; translational
Cita
Mondaza JL,Amian R,Antonio Cordero Varela J,Carrera MA,Rodriguez MC,Lopez M,Villar VH,Ramos R,Valverde C,Cruz J,Martinez J,DIAZ R,Hindi N,Fernandez A,Lopez JA,Moura DS,Martin J. Biomarkers of prognosis and pazopanib response in soft tissue sarcoma: An exploratory analysis. Ther. Adv. Med. Oncol. 2026. 18. 17588359261474856. IF:4,100. (2).