Department of Orthopedics, the First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China.
Department of Nephrology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, P.R. China.
Scand J Clin Lab Invest. 2019 Dec;79(8):601-612. doi: 10.1080/00365513.2019.1683764. Epub 2019 Oct 30.
Osteosarcoma is a malignant bone tumor with extremely high invasion, metastasis and mortality. The prognosis of patients with osteosarcoma remains poor. The ErbB receptor family was found to be overexpressed in human cancers and associated with poor prognosis. However, the role of ErbB receptor family in osteosarcoma has not been fully understood. The present study aimed to investigate the clinicopathological and prognostic significances of ErbB receptors in primary osteosarcoma. Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) were used to detect the protein and gene expression of ErbB receptors in 60 primary osteosarcoma specimens and 30 non-neoplastic bone tissues. WB and RT-qPCR analyses showed that the protein and mRNA expression levels of EGFR, ErbB3 and ErbB4 in osteosarcoma specimens were significantly higher than those in non-neoplastic bone tissues. Seventeen (28.33%), 15 (25.00%) and 15 (25.00%) osteosarcoma specimens presented with amplification of EGFR, ErbB3 and ErbB4 gene, respectively, which were significantly higher compared with non-neoplastic bone tissues. The amplification of ErbB3 and ErbB4 in osteosarcoma was associated with advanced surgical stage. The amplification of EGFR, ErbB3, ErbB4 and the co-amplification of EGFR-ErbB3, EGFR-ErbB4, ErbB3-ErbB4 was linked with poor response to chemotherapy and distant metastasis. The amplification of EGFR, ErbB3 and ErbB4, as well as their co-amplification demonstrated independent prognostic values for reduced survival time of osteosarcoma patients and may serve as potential therapeutic targets for osteosarcoma patients in the future.
骨肉瘤是一种恶性骨肿瘤,具有极高的侵袭性、转移性和死亡率。骨肉瘤患者的预后仍然较差。研究发现,表皮生长因子受体(ErbB)家族在人类癌症中过度表达,并与不良预后相关。然而,ErbB 受体家族在骨肉瘤中的作用尚未完全阐明。本研究旨在探讨 ErbB 受体在原发性骨肉瘤中的临床病理和预后意义。采用 Western blot(WB)、逆转录定量聚合酶链反应(RT-qPCR)和荧光原位杂交(FISH)检测 60 例原发性骨肉瘤标本和 30 例非肿瘤性骨组织中 ErbB 受体的蛋白和基因表达。WB 和 RT-qPCR 分析显示,骨肉瘤标本中 EGFR、ErbB3 和 ErbB4 的蛋白和 mRNA 表达水平明显高于非肿瘤性骨组织。17 例(28.33%)、15 例(25.00%)和 15 例(25.00%)骨肉瘤标本 EGFR、ErbB3 和 ErbB4 基因扩增,明显高于非肿瘤性骨组织。骨肉瘤中 ErbB3 和 ErbB4 的扩增与手术分期较晚有关。EGFR、ErbB3、ErbB4 的扩增以及 EGFR-ErbB3、EGFR-ErbB4、ErbB3-ErbB4 的共扩增与对化疗反应不良和远处转移有关。EGFR、ErbB3 和 ErbB4 的扩增及其共扩增对骨肉瘤患者的生存时间有独立的预后价值,可能成为骨肉瘤患者未来潜在的治疗靶点。