Zhang Caiqing, Kang Yanmeng, Ma Ruiping, Chen Feng, Chen Fangfang, Dong Xueli
Department of Respiratory Medicine, Shandong Provincial Qianfoshan Hospital, Jinan 250014, Shandong Province, China.
Department of Liver Disease, Shandong Provincial Qianfoshan Hospital, Jinan 250014, Shandong Province, China.
J Cancer Res Ther. 2018 Jul-Sep;14(5):970-976. doi: 10.4103/0973-1482.180614.
Malignant pleural mesothelioma (MPM) is a highly lethal and refractory to multimodal treatment tumor. Numb is considered as a tumor suppressor playing critical roles in determining cell fate and has been shown to target the oncogenic transcription factor Gli1 for Itch-dependent ubiquitination, resulting in suppression of the oncogenic sonic hedgehog signaling in medulloblastoma. This study was designed to analysis the role of Numb and Gli1 in MPM.
Tissues of 61 MPM patients and 22 normal pleura as control were investigated. Numb and Gli1 expression were evaluated by immunohistochemistry. The associations with clinical and pathological parameters of the two markers were statistically analyzed, and the correlation between them was also demonstrated.
The expression levels of Numb with nuclear Gli1 exhibited a significant inverse correlation (r = -0.361 P < 0.05). In addition, Numb has an inverse correlation with ki-67 labeling index (P < 0.05), and nuclear Gli1 was found in associated with the tumor International Mesothelioma Interest Group-stage (P < 0.05). The overall survival was influenced by the expression of Numb (P < 0.05) and histological subtype (P < 0.05), further regression analysis showed that only histological subtype has a prognostic influence on survival (P < 0.05).
The results provide new evidence of Numb and Gli1 on the clinical characteristics of MPM, which may be helpful in clinical diagnosis and targeted therapy. Further research with larger sample size is needed.
恶性胸膜间皮瘤（MPM）是一种具有高度致死性且对多模式治疗耐药的肿瘤。Numb被认为是一种肿瘤抑制因子，在决定细胞命运中起关键作用，并且已被证明可靶向致癌转录因子Gli1进行Itch依赖的泛素化，从而抑制髓母细胞瘤中的致癌性声波刺猬信号通路。本研究旨在分析Numb和Gli1在MPM中的作用。
研究了61例MPM患者的组织以及22例作为对照的正常胸膜组织。通过免疫组织化学评估Numb和Gli1的表达。对这两种标志物与临床和病理参数的相关性进行统计学分析，并证明它们之间的相关性。
Numb与核Gli1的表达水平呈显著负相关（r = -0.361，P < 0.05）。此外，Numb与ki-67标记指数呈负相关（P < 0.05），并且发现核Gli1与肿瘤国际间皮瘤兴趣小组分期相关（P < 0.05）。总生存期受Numb表达（P < 0.05）和组织学亚型（P < 0.05）的影响，进一步的回归分析表明只有组织学亚型对生存期有预后影响（P < 0.05）。
结果为Numb和Gli1在MPM临床特征方面提供了新证据，这可能有助于临床诊断和靶向治疗。需要更大样本量的进一步研究。
