Huang Qin, Yan Xiaorong, Zhang Bo, Liu Zelin, Chen Yongjian, Liu Xiaohai, Li Mingchu, Su Xin, Wang Xianlong, Wu Bowen, Chen Ge, Pan Jun, Lin Zhixiong, Chen Yiguang
Department of Neurosurgery, Nanfang Hospital, Southern Medical University, No. 1838, Guangzhou North Road, Guangzhou, Guangdong, China.
Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian, China.
Pituitary. 2025 Jul 1;28(4):80. doi: 10.1007/s11102-025-01552-x.
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.
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.
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).
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.
造釉细胞瘤型颅咽管瘤（ACP）是一种组织学上为良性但临床上具有侵袭性的颅内肿瘤，其特点是复发率高。成纤维细胞活化蛋白（FAP）是癌症相关成纤维细胞（CAFs）的标志物，与肿瘤进展和微环境重塑有关。本研究评估了FAP的预后意义，并开发了一种基于放射组学的模型用于术前非侵入性风险分层。
对54例ACP病例进行免疫组织化学分析，以评估FAP表达水平。分析来自两个外部数据库的110例ACP病例的转录组数据，以进行差异基因表达和通路富集分析。进行免疫荧光检测以确定FAP与血管生成标志物（VEGF、CD31、CD34）的空间相关性。利用术前MRI数据开发一个放射组学模型来预测FAP表达，并对其预测性能进行验证。
高FAP表达与细胞外基质重塑、血管生成和炎症通路激活相关。临床上，高FAP表达的肿瘤体积更大（P = 0.044），下丘脑功能障碍更严重（P = 0.001），无进展生存期更短（P = 0.03）。多变量分析确定高FAP表达（HR = 9.890，P = 0.0340）是复发的独立预测因子。免疫荧光证实FAP CAFs与血管生成标志物共定位，提示其在肿瘤复发中的作用。整合T1/T2加权MRI特征的放射组学模型在预测FAP表达方面表现出强大性能，训练集、内部验证集和外部验证集的AUC分别为0.742、0.822和0.686。
FAP是ACP的一种预后生物标志物，高表达表明复发风险增加。放射组学模型为术前风险分层提供了一种非侵入性方法，可能指导手术决策和抗血管生成治疗策略。
