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成纤维细胞激活蛋白过表达与骨肉瘤患者的临床意义。

Overexpression of fibroblast activation protein and its clinical implications in patients with osteosarcoma.

机构信息

Department of Orthopedics, Huaían First People's Hospital, Nanjing Medical University, Huaían, Jiangsu, PR China.

出版信息

J Surg Oncol. 2013 Sep;108(3):157-62. doi: 10.1002/jso.23368. Epub 2013 Jun 28.

DOI:10.1002/jso.23368
PMID:23813624
Abstract

BACKGROUND AND OBJECTIVES

Fibroblast activation protein (FAP) expression has been detected in fibroblastic component of osteosarcomas. The aim of this study was to analyze the correlation of FAP expression with the clinicopathological features of osteosarcoma.

METHODS

FAP mRNA and protein expression levels in human osteosarcoma tissues were, respectively detected by RT-PCR, Western blot, and immunohistochemistry assays.

RESULTS

FAP mRNA and protein expression were both higher in osteosarcoma than in corresponding noncancerous bone tissues (both P < 0.001). In addition, the immunohistochemistry assay found that all patients showed positive FAP expression. Higher FAP expression was significantly correlated with advanced clinical stage (P = 0.006), high histological grade (P = 0.02), positive metastatic status (P = 0.01), shorter overall (P < 0.001), and disease-free (P < 0.001) survival in osteosarcoma patients. Furthermore, Cox multivariate analysis showed that FAP overexpression was an independent prognostic factor for predicting both overall and disease-free survival of osteosarcoma patients.

CONCLUSION

Expression of FAP in osteosarcoma could be adopted as a candidate biomarker for the diagnosis of clinical stage, histological grade and metastasis, and for assessing prognosis, indicating for the first time that FAP may play an important role in tumor development and progression in osteosarcoma. FAP might be considered as a novel therapeutic target against this cancer.

摘要

背景与目的

成纤维细胞激活蛋白(FAP)在骨肉瘤的成纤维细胞成分中被检测到表达。本研究旨在分析 FAP 表达与骨肉瘤临床病理特征的相关性。

方法

采用 RT-PCR、Western blot 和免疫组织化学检测人骨肉瘤组织中 FAP mRNA 和蛋白的表达水平。

结果

FAP mRNA 和蛋白在骨肉瘤中的表达均高于相应的非癌性骨组织(均 P<0.001)。此外,免疫组织化学检测发现所有患者均显示 FAP 阳性表达。较高的 FAP 表达与晚期临床分期(P=0.006)、高组织学分级(P=0.02)、阳性转移状态(P=0.01)、骨肉瘤患者总生存期(P<0.001)和无病生存期(P<0.001)较短显著相关。此外,Cox 多因素分析显示,FAP 过表达是预测骨肉瘤患者总生存期和无病生存期的独立预后因素。

结论

骨肉瘤中 FAP 的表达可作为临床分期、组织学分级和转移的诊断候选生物标志物,并可评估预后,首次表明 FAP 可能在骨肉瘤的肿瘤发生和进展中发挥重要作用。FAP 可能被认为是针对这种癌症的一种新的治疗靶点。

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