Crane Jacquelyn N, Graham Danielle S, Mona Christine E, Nelson Scott D, Samiei Alireza, Dawson David W, Dry Sarah M, Masri Marwan G, Crompton Joseph G, Benz Matthias R, Czernin Johannes, Eilber Fritz C, Graeber Thomas G, Calais Jeremie, Federman Noah C
Department of Pediatrics, Division of Pediatric Hematology, Oncology, Stem Cell Transplantation & Regenerative Medicine, Stanford University School of Medicine, 1000 Welch Rd, Suite 300, Palo Alto, CA 94304, USA.
University of California Los Angeles, Department of Surgery, Los Angeles, CA, USA.
Sarcoma. 2023 Jun 9;2023:2480493. doi: 10.1155/2023/2480493. eCollection 2023.
Fibroblast activation protein alpha (FAP) is highly expressed by cancer-associated fibroblasts in multiple epithelial cancers. The aim of this study was to characterize FAP expression in sarcomas to explore its potential utility as a diagnostic and therapeutic target and prognostic biomarker in sarcomas.
Available tissue samples from patients with bone or soft tissue tumors were identified at the University of California, Los Angeles. FAP expression was evaluated via immunohistochemistry (IHC) in tumor samples ( = 63), adjacent normal tissues ( = 30), and positive controls ( = 2) using semiquantitative systems for intensity (0 = negative; 1 = weak; 2 = moderate; and 3 = strong) and density (none, <25%, 25-75%; >75%) in stromal and tumor/nonstromal cells and using a qualitative overall score (not detected, low, medium, and high). Additionally, RNA sequencing data in publicly available databases were utilized to compare FAP expression in samples ( = 10,626) from various cancer types and evaluate the association between FAP expression and overall survival (OS) in sarcoma ( = 168).
The majority of tumor samples had FAP IHC intensity scores ≥2 and density scores ≥25% for stromal cells (77.7%) and tumor cells (50.7%). All desmoid fibromatosis, myxofibrosarcoma, solitary fibrous tumor, and undifferentiated pleomorphic sarcoma samples had medium or high FAP overall scores. Sarcomas were among cancer types with the highest mean FAP expression by RNA sequencing. There was no significant difference in OS in patients with sarcoma with low versus high FAP expression.
The majority of the sarcoma samples showed FAP expression by both stromal and tumor/nonstromal cells. Further investigation of FAP as a potential diagnostic and therapeutic target in sarcomas is warranted.
成纤维细胞活化蛋白α（FAP）在多种上皮性癌症的癌症相关成纤维细胞中高度表达。本研究的目的是描述FAP在肉瘤中的表达特征，以探索其作为肉瘤诊断和治疗靶点以及预后生物标志物的潜在用途。
在加利福尼亚大学洛杉矶分校识别出患有骨或软组织肿瘤患者的可用组织样本。通过免疫组织化学（IHC）使用半定量系统评估肿瘤样本（n = 63）、相邻正常组织（n = 30）和阳性对照（n = 2）中FAP的表达，评估基质细胞和肿瘤/非基质细胞中的强度（0 = 阴性；1 = 弱；2 = 中等；3 = 强）和密度（无、<25%、25 - 75%；>75%），并使用定性总体评分（未检测到、低、中、高）。此外，利用公开可用数据库中的RNA测序数据比较来自各种癌症类型的样本（n = 10,626）中FAP的表达，并评估FAP表达与肉瘤（n = 168）总生存期（OS）之间的关联。
大多数肿瘤样本的基质细胞（77.7%）和肿瘤细胞（50.7%）的FAP IHC强度评分≥2且密度评分≥25%。所有韧带样纤维瘤病、黏液纤维肉瘤、孤立性纤维性肿瘤和未分化多形性肉瘤样本的FAP总体评分均为中等或高。肉瘤是通过RNA测序显示平均FAP表达最高的癌症类型之一。FAP表达低与高的肉瘤患者的OS无显著差异。
大多数肉瘤样本的基质细胞和肿瘤/非基质细胞均显示FAP表达。有必要进一步研究FAP作为肉瘤潜在诊断和治疗靶点的作用。
