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原发性骨肉瘤患者中Gasdermin D的表达及临床病理结果

Gasdermin D expression and clinicopathologic outcome in primary osteosarcoma patients.

作者信息

Lin Rongjin, Wei Hongxiang, Wang Shenglin, Huang Zhen, Chen Hui, Zhang Shaoying, Lin Jianhua, Zhong Guangxian

机构信息

Department of Nursing, The First Affiliated Hospital of Fujian Medical University Fuzhou 350005, Fujian, PR China.

Department of Orthopedics, The First Affiliated Hospital of Fujian Medical University Fuzhou, Fujian, China.

出版信息

Int J Clin Exp Pathol. 2020 Dec 1;13(12):3149-3157. eCollection 2020.

Abstract

Gasdermin D (GSDMD), a recently discovered pyroptosis-related protein, has been extensively studied in inflammatory diseases. Research has indicated that inflammation is a causative factor of malignant tumors, including osteosarcoma. Nevertheless, the specific functions of GSDMD in osteosarcoma have not well been studied. This study aimed to explore the clinicopathologic values of GSDMD in osteosarcoma. The expression of GSDMD protein in 41 samples of primary osteosarcoma and 20 normal bone tissues were evaluated by immunohistochemistry and western blot. The χ test and Student's t test were applied to analyze the differences of GSDMD expression between osteosarcoma and normal bone tissues. The χ test and Fisher's exact test were used to assess the associations of GSDMD expression with clinicopathologic characteristics of osteosarcoma patients. Moreover, the Kaplan-Meier and Cox regression model methods were used to analyze the relations between GSDMD expression and disease-free survival (DFS) and overall survival (OS) of osteosarcoma patients. The GSDMD protein was significantly overexpressed in osteosarcoma compared to non-neoplastic bone samples. Additionally, GSDMD overexpression was related to poor chemotherapy response ( = 0.031), distant metastasis ( < 0.001), as well as worse prognosis of osteosarcoma patients. Furthermore, GSDMD protein overexpression was an independent predictor of poor survival time in primary osteosarcoma patients. In conclusion, GSDMD overexpression was related to adverse clinical outcome of osteosarcoma, and could be a therapy target in osteosarcoma. Further study should focus on the related mechanism of GSDMD in osteosarcoma.

摘要

Gasdermin D(GSDMD)是一种最近发现的与细胞焦亡相关的蛋白质,已在炎症性疾病中得到广泛研究。研究表明,炎症是包括骨肉瘤在内的恶性肿瘤的致病因素。然而,GSDMD在骨肉瘤中的具体功能尚未得到充分研究。本研究旨在探讨GSDMD在骨肉瘤中的临床病理价值。通过免疫组织化学和蛋白质印迹法评估了41例原发性骨肉瘤样本和20例正常骨组织中GSDMD蛋白的表达。应用χ检验和Student's t检验分析骨肉瘤与正常骨组织中GSDMD表达的差异。采用χ检验和Fisher精确检验评估GSDMD表达与骨肉瘤患者临床病理特征的相关性。此外,使用Kaplan-Meier法和Cox回归模型分析GSDMD表达与骨肉瘤患者无病生存期(DFS)和总生存期(OS)之间的关系。与非肿瘤性骨样本相比,GSDMD蛋白在骨肉瘤中显著过表达。此外,GSDMD过表达与化疗反应差(P = 0.031)、远处转移(P < 0.001)以及骨肉瘤患者预后较差有关。此外,GSDMD蛋白过表达是原发性骨肉瘤患者生存时间差的独立预测因素。总之,GSDMD过表达与骨肉瘤的不良临床结局相关,可能是骨肉瘤的治疗靶点。进一步的研究应聚焦于GSDMD在骨肉瘤中的相关机制。

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