Department of Orthopaedic Surgery, The Affiliated Drum Tower Hospital of Nanjing, University Medical School, Nanjing, Jaingsu, P.R. China.
J Surg Oncol. 2012 Mar;105(3):235-43. doi: 10.1002/jso.22077. Epub 2011 Aug 22.
The aim of this study was to investigate the association of insulin-like growth factor-1 receptor (IGF-1R) with metastasis and prognosis of osteosarcoma patients.
RT-PCR and Western blot assays were performed to detect IGF-1R mRNA and protein expression in 26 osteosarcoma and noncancerous bone tissues. Immunohistochemistry was performed to analyze the correlation of IGF-1R expression in 84 osteosarcoma tissues with clinicopathological factors or survival of patients. Lentivirus-mediated RNA interference system was employed to downregulate IGF-1R expression and analyze the effects of IGF-1R downregulation on invasion and metastasis of osteosarcoma cells.
The relative levels of IGF-1R mRNA and protein expression were significantly higher in osteosarcoma tissues than in corresponding noncancerous bone tissues. The expression of IGF-1R protein was closely associated with surgical stage and distant metastasis of osteosarcoma patients. Osteosarcoma patients with high IGF-1R expression had poorer survival, and multivariate Cox analyses showed that high IGF-1R expression was an independent prognostic maker. Lentivirus-mediated targeting IGF-1R could significantly inhibit adhesion, migration, invasion, and metastasis of osteosarcoma cells, which might be correlated with of inactivation of Akt signaling pathway.
IGF-1R is an independent prognostic marker for osteosarcoma patients and increased expression of this molecular is correlated with metastasis of osteosarcoma.
本研究旨在探讨胰岛素样生长因子-1 受体(IGF-1R)与骨肉瘤患者转移和预后的关系。
采用 RT-PCR 和 Western blot 法检测 26 例骨肉瘤组织和非癌骨组织中 IGF-1R mRNA 和蛋白的表达。采用免疫组化法分析 84 例骨肉瘤组织中 IGF-1R 表达与患者临床病理因素及生存的相关性。采用慢病毒介导的 RNA 干扰系统下调 IGF-1R 表达,分析 IGF-1R 下调对骨肉瘤细胞侵袭和转移的影响。
骨肉瘤组织中 IGF-1R mRNA 和蛋白的相对表达水平明显高于相应的非癌骨组织。IGF-1R 蛋白的表达与骨肉瘤患者的手术分期和远处转移密切相关。高 IGF-1R 表达的骨肉瘤患者生存较差,多因素 Cox 分析表明高 IGF-1R 表达是独立的预后标志物。慢病毒介导的靶向 IGF-1R 可显著抑制骨肉瘤细胞的黏附、迁移、侵袭和转移,这可能与 Akt 信号通路失活有关。
IGF-1R 是骨肉瘤患者的独立预后标志物,该分子的高表达与骨肉瘤的转移有关。