Li Xiao-Ming, Lin Wei, Wang Jiang, Zhang Wei, Yin An-An, Huang Yi, Zhang Jian, Yao Libo, Bian Huan, Zhang Jing, Zhang Xiang
Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
Mol Med Rep. 2016 Dec;14(6):5626-5636. doi: 10.3892/mmr.2016.5921. Epub 2016 Nov 3.
Differentiated embryo chondrocyte expressed gene 1 (Dec1), a crucial cell differentiation mediator and apoptosis inhibitor, is abundantly expressed in various types of human cancer and is associated with malignant tumor progression. As poor differentiation and low apoptosis are closely associated with poor survival rates and a poor response to radio/chemotherapy in patients with cancer, the prognostic value of Dec1 expression was examined in the present study and its correlation with response to temozolomide (TMZ) chemotherapy was analyzed in patients with glioma. Dec1 expression was analyzed by immunohistochemistry in 157 samples of newly diagnosed glioma and 63 recurrent glioblastoma cases that relapsed during TMZ chemotherapy. Correlations with clinical variables, prognosis and the response to TMZ chemotherapy were analyzed in the newly diagnosed gliomas. Dec1 expression was also compared with the apoptosis index determined by TdT‑mediated dUTP nick ending‑labeling assay in recurrent glioblastomas. The antiglioma effect of TMZ in nude mice xenografts with Dec1 expression was examined in vivo. High expression of Dec1, which was significantly associated with high pathological tumor grade and poor response to TMZ chemotherapy, was demonstrated to be an unfavorable independent prognostic factor and predicted poor survival in patients with newly diagnosed glioma. In patients with recurrent glioblastoma, there was a negative correlation between Dec1 expression and the apoptotic index. In nude mice treated with TMZ, Dec1 overexpression potentiated proliferation, but attenuated TMZ‑induced apoptosis. In conclusion, Dec1 is a prognostic factor for the clinical outcome and a predictive factor for the response to TMZ chemotherapy in patients with glioma.
分化型胚胎软骨细胞表达基因1（Dec1）是一种关键的细胞分化调节因子和凋亡抑制因子，在多种人类癌症中大量表达，并与恶性肿瘤进展相关。由于分化差和凋亡率低与癌症患者的低生存率及对放疗/化疗的不良反应密切相关，本研究检测了Dec1表达的预后价值，并分析了其与胶质瘤患者替莫唑胺（TMZ）化疗反应的相关性。采用免疫组织化学方法分析了157例新诊断胶质瘤样本和63例在TMZ化疗期间复发的复发性胶质母细胞瘤病例中的Dec1表达。分析新诊断胶质瘤中Dec1表达与临床变量、预后及TMZ化疗反应的相关性。还将复发性胶质母细胞瘤中Dec1的表达与通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记法测定的凋亡指数进行比较。在体内检测了TMZ对Dec1表达的裸鼠异种移植瘤的抗胶质瘤作用。结果表明，Dec1的高表达与高病理肿瘤分级及对TMZ化疗的不良反应显著相关，是新诊断胶质瘤患者不良的独立预后因素，并预示着较差的生存率。在复发性胶质母细胞瘤患者中，Dec1表达与凋亡指数呈负相关。在用TMZ治疗的裸鼠中，Dec1过表达增强了增殖，但减弱了TMZ诱导的凋亡。总之，Dec1是胶质瘤患者临床结局的预后因素和TMZ化疗反应的预测因素。
