Department of Orthopaedic Surgery, Chonbuk National University Medical School, Research Institute of Clinical Medicine and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea.
PLoS One. 2013 Sep 3;8(9):e74738. doi: 10.1371/journal.pone.0074738. eCollection 2013.
Recently, the roles of SIRT1 and deleted in breast cancer 1 (DBC1) in human cancer have been extensively studied and it has been demonstrated that they are involved in many human carcinomas. However, their clinical significance for soft-tissue sarcomas has not been examined. In this study, we evaluated the expression and prognostic significance of the expression of SIRT1, DBC1, P53, β-catenin, cyclin D1, and KI67 in 104 cases of soft-tissue sarcomas.
Immunohistochemical expression of SIRT1, DBC1, P53, β-catenin, and cyclin D1 were seen in 71%, 74%, 53%, 48%, and 73% of sarcomas, respectively. The expression of SIRT1, DBC1, P53, β-catenin, and cyclin D1 were significantly correlated with advanced clinicopathological parameters such as higher clinical stage, higher histological grade, increased mitotic counts, and distant metastasis. The expression of SIRT1, DBC1, P53, β-catenin, cyclin D1, and KI67 were significantly correlated with each other and positive expression of all of these predicted shorter overall survival and event-free survival by univariate analysis. Multivariate analysis revealed the expression of SIRT1 as an independent prognostic indicator for overall survival and event-free survival of sarcoma patients. In conclusion, this study demonstrates that SIRT1- and DBC1-related pathways may be involved in the progression of soft-tissue sarcomas and can be used as clinically significant prognostic indicators for sarcoma patients. Moreover, the SIRT1- and DBC1-related pathways could be new therapeutic targets for the treatment of sarcomas.
最近，SIRT1 和乳腺癌 1 缺失物（DBC1）在人类癌症中的作用得到了广泛研究，研究表明它们参与了许多人类癌。然而，它们对软组织肉瘤的临床意义尚未得到检验。在这项研究中，我们评估了 SIRT1、DBC1、P53、β-连环蛋白、细胞周期蛋白 D1 和 KI67 在 104 例软组织肉瘤中的表达及其预后意义。
免疫组化显示，71%的肉瘤表达 SIRT1，74%的肉瘤表达 DBC1，53%的肉瘤表达 P53，48%的肉瘤表达 β-连环蛋白，73%的肉瘤表达细胞周期蛋白 D1。SIRT1、DBC1、P53、β-连环蛋白和细胞周期蛋白 D1 的表达与高级临床病理参数显著相关，如临床分期较高、组织学分级较高、有丝分裂计数增加和远处转移。SIRT1、DBC1、P53、β-连环蛋白、细胞周期蛋白 D1 和 KI67 的表达相互显著相关，单因素分析显示所有这些的阳性表达均预示着总生存率和无事件生存率较短。多因素分析显示，SIRT1 的表达是软组织肉瘤患者总生存率和无事件生存率的独立预后指标。总之，本研究表明 SIRT1 和 DBC1 相关途径可能参与了软组织肉瘤的进展，可作为软组织肉瘤患者具有临床意义的预后指标。此外，SIRT1 和 DBC1 相关途径可能成为治疗肉瘤的新的治疗靶点。
