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

IF 3.3 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Qin Huang, Xiaorong Yan, Bo Zhang, Zelin Liu, Yongjian Chen, Xiaohai Liu, Mingchu Li, Xin Su, Xianlong Wang, Bowen Wu, Ge Chen, Jun Pan, Zhixiong Lin, Yiguang Chen
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引用次数: 0

Abstract

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.

FAP作为adamadaminomous颅咽管瘤血管生成相关复发的预后生物标志物和放射组学预测因子。
背景:金刚素瘤性颅咽管瘤(ACP)是一种组织学上良性但临床上具有侵袭性的颅内肿瘤,复发率高。成纤维细胞激活蛋白(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无创术前风险分层模型。方法:对54例ACP患者行免疫组化分析,检测FAP表达水平。通过两个外部数据库对110例ACP病例的转录组学数据进行了差异基因表达和途径富集分析。采用免疫荧光法测定FAP与血管生成标志物(VEGF、CD31、CD34)的空间相关性。利用术前MRI数据建立放射组学模型来预测FAP表达,并验证其预测性能。结果:FAP高表达与细胞外基质重塑、血管生成和炎症通路激活有关。临床上,高fap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)。多因素分析发现高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起作用。整合T1/ t2加权MRI特征的放射组学模型在预测FAP表达方面表现出稳健的性能,auc为0.742(训练集),0.822(内部验证集)和0.686(外部验证集)。结论:FAP是ACP的预后生物标志物,其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无创方法,可能指导手术决策和抗血管生成治疗策略。
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来源期刊
Pituitary
Pituitary 医学-内分泌学与代谢
CiteScore
7.10
自引率
7.90%
发文量
90
审稿时长
6 months
期刊介绍: Pituitary is an international publication devoted to basic and clinical aspects of the pituitary gland. It is designed to publish original, high quality research in both basic and pituitary function as well as clinical pituitary disease. The journal considers: Biology of Pituitary Tumors Mechanisms of Pituitary Hormone Secretion Regulation of Pituitary Function Prospective Clinical Studies of Pituitary Disease Critical Basic and Clinical Reviews Pituitary is directed at basic investigators, physiologists, clinical adult and pediatric endocrinologists, neurosurgeons and reproductive endocrinologists interested in the broad field of the pituitary and its disorders. The Editorial Board has been drawn from international experts in basic and clinical endocrinology. The journal offers a rapid turnaround time for review of manuscripts, and the high standard of the journal is maintained by a selective peer-review process which aims to publish only the highest quality manuscripts. Pituitary will foster the publication of creative scholarship as it pertains to the pituitary and will provide a forum for basic scientists and clinicians to publish their high quality pituitary-related work.
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