FAP as a prognostic biomarker and radiomics-based predictor of angiogenesis-associated recurrence in Adamantinomatous craniopharyngioma.

Background: Adamantinomatous craniopharyngioma (ACP) is a histologically benign yet clinically aggressive intracranial tumor characterized by high recurrence rates. Fibroblast activation protein (FAP), a marker of cancer-associated fibroblasts (CAFs), is implicated in tumor progression and microenvironment remodeling. This study evaluates the prognostic significance of FAP and develops a radiomics-based model for non-invasive preoperative risk stratification.

Methods: Immunohistochemical analysis was performed on 54 ACP cases to assess FAP expression levels. Transcriptomic data from 110 ACP cases across two external databases were analyzed for differential gene expression and pathway enrichment. Immunofluorescence was conducted to determine the spatial correlation of FAP with angiogenic markers (VEGF, CD31, CD34). A radiomics model was developed using preoperative MRI data to predict FAP expression and validated for predictive performance.

Results: High FAP expression was associated with extracellular matrix remodeling, angiogenesis, and inflammatory pathway activation. Clinically, high-FAP tumors exhibited larger volumes (P = 0.044), more severe hypothalamic dysfunction (P = 0.001), and shorter progression-free survival (P = 0.03). Multivariate analysis identified high FAP expression (HR = 9.890, P = 0.0340) as an independent predictor of recurrence. Immunofluorescence confirmed the co-localization of FAP CAFs with angiogenic markers, suggesting a role in tumor recurrence. The radiomics model integrating T1/T2-weighted MRI features demonstrated robust performance in predicting FAP expression, with AUCs of 0.742 (training set),0.822 (internal validation set) and 0.686(external validation set).

Conclusions: FAP is a prognostic biomarker in ACP, with high expression indicative of increased recurrence risk. The radiomics model offers a non-invasive approach for preoperative risk stratification, potentially guiding surgical decision-making and anti-angiogenic therapeutic strategies.