Gastric cancer fibroblasts affect the effect of immunotherapy and patient prognosis by inducing micro-vascular production.
Front Immunol
; 15: 1375013, 2024.
Article
en En
| MEDLINE
| ID: mdl-39040110
ABSTRACT
Introduction:
Immunotherapy is critical for treating many cancers, and its therapeutic success is linked to the tumor microenvironment. Although anti-angiogenic drugs are used to treat gastric cancer (GC), their efficacy remains limited. Cancer-associated fibroblast (CAF)-targeted therapies complement immunotherapy; however, the lack of CAF-specific markers poses a challenge. Therefore, we developed a CAF angiogenesis prognostic score (CAPS) system to evaluate prognosis and immunotherapy response in patients with GC, aiming to improve patient stratification and treatment efficacy.Methods:
We assessed patient-derived GC CAFs for promoting angiogenesis using EdU, cell cycle, apoptosis, wound healing, and angiogenesis analysis.Results:
We then identified CAF-angiogenesis-associated differentially-expressed genes, leading to the development of CAPS, which included THBS1, SPARC, EDNRA, and VCAN. We used RT-qPCR to conduct gene-level validation, and eight GEO datasets and the HPA database to validate the CAPS system at the gene and protein levels. Six independent GEO datasets were utilized for validation. Overall survival time was shorter in the high- than the low-CAPS group. Immune microenvironment and immunotherapy response analysis showed that the high-CAPS group had a greater tendency toward immune escape and reduced immunotherapy efficacy than the low-CAPS group.Discussion:
CAPS is closely associated with GC prognosis and immunotherapy outcomes. It is therefore an independent predictor of GC prognosis and immunotherapy efficacy.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Gástricas
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Microambiente Tumoral
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Fibroblastos Asociados al Cáncer
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Inmunoterapia
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Neovascularización Patológica
Límite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Front Immunol
Año:
2024
Tipo del documento:
Article
País de afiliación:
China