Department of Orthopaedics, Huai'an Hospital, Xuzhou Medical College, Huai'an, People's Republic of China.
Med Oncol. 2010 Dec;27(4):1239-45. doi: 10.1007/s12032-009-9365-y. Epub 2009 Nov 20.
The mTOR/p70S6K signal transduction pathway plays a key role in the regulation of cancer cells' survival and proliferation. However, its roles in osteosarcoma, which is one of the most rapidly growing sarcomas, remain unknown. This study investigated for the first time the correlation between the mTOR/p70S6K signal transduction pathway in human osteosarcoma and patients' prognosis. The expression patterns of mTOR and p70S6K in paraffin-embedded specimens gathered from 65 patients with primary osteosarcoma were detected by the method of immunohistochemistry using antibodies against mTOR and p70S6K. Kaplan-Meier survival and Cox regression analyses were performed to evaluate the prognosis of patients. Immunostaining revealed that the mTOR/p70S6K signal transduction pathway is activated in human osteosarcoma. Additionally, positive expression of mTOR and p70S6K proteins was significantly correlated with surgical stage, metastasis pattern and percentage of dead cells of osteosarcoma. Moreover, in univariate analysis, surgical stage, metastasis pattern and percentage of dead cells, mTOR and p70S6K expression showed significant influence on overall survival (OS) and disease-free survival (DFS). In multivariate analysis, surgical stage (IIA vs. IIB/III), metastasis pattern (without vs. with), percentage of dead cells (≥90 vs. <90%), mTOR expression pattern (negative vs. positive) and p70S6K expression pattern (negative vs. positive) were significant for DFS and OS. Our results demonstrate the correlation of mTOR and p70S6K expression patterns with the oncological progression of osteosarcoma patients, suggesting the prognostic significance of the mTOR/p70S6K signal transduction pathway in osteosarcoma patients, which may lay a foundation for making further investigations on the mTOR/p70S6K signal transduction pathway as a potential target for osteosarcoma therapy.
mTOR/p70S6K 信号转导通路在调节癌细胞的存活和增殖中起着关键作用。然而，其在骨肉瘤中的作用仍不清楚，骨肉瘤是生长最快的肉瘤之一。本研究首次探讨了人骨肉瘤中 mTOR/p70S6K 信号转导通路与患者预后的相关性。采用 mTOR 和 p70S6K 抗体的免疫组织化学方法检测 65 例原发性骨肉瘤石蜡包埋标本中 mTOR 和 p70S6K 的表达模式。采用 Kaplan-Meier 生存分析和 Cox 回归分析评估患者的预后。免疫组化结果显示 mTOR/p70S6K 信号转导通路在人骨肉瘤中被激活。此外，mTOR 和 p70S6K 蛋白的阳性表达与骨肉瘤的手术分期、转移模式和骨肿瘤细胞死亡率显著相关。此外，单因素分析显示，手术分期、转移模式和骨肿瘤细胞死亡率、mTOR 和 p70S6K 表达对总生存期（OS）和无病生存期（DFS）有显著影响。多因素分析显示，手术分期（IIA 期与 IIB/III 期）、转移模式（无转移与有转移）、骨肿瘤细胞死亡率（≥90%与<90%）、mTOR 表达模式（阴性与阳性）和 p70S6K 表达模式（阴性与阳性）与 DFS 和 OS 显著相关。本研究结果表明，mTOR 和 p70S6K 表达模式与骨肉瘤患者的肿瘤进展相关，提示 mTOR/p70S6K 信号转导通路在骨肉瘤患者中的预后意义，为进一步研究 mTOR/p70S6K 信号转导通路作为骨肉瘤治疗的潜在靶点奠定了基础。
