Guo Zonghui, Tang Yin, Fu Youwei, Wang Junjie
Department of Orthopedics, Ningbo No.2 Hospital, Ningbo, Zhejiang 315000, China.
Department of Orthopedics, Ningbo No.2 Hospital, Ningbo, Zhejiang 315000, China.
Pathol Res Pract. 2019 Mar;215(3):519-524. doi: 10.1016/j.prp.2019.01.008. Epub 2019 Jan 7.
Signal transducer and activator of transcription 5 (STAT5) plays a key role in the malignancy of many tumors and has been identified as a therapeutic target. However, the role of STAT5A in osteosarcoma is still unclear.
98 osteosarcoma patients were obtain from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET). The relationship between STAT5A and clinical features was analyzed using the Wilcoxon signed-rank test and logistic regression. Kaplan-Meier method, univariate and multivariate Cox regression analyses were performed to assess the prognostic value in event-free survival (EFS) and overall survival (OS). Gene Set Enrichment Analysis (GSEA) was performed.
STAT5A low expression was not linked to age, gender, tumor site, surgical approach, tumor region, histologic response, and metastasis, but was correlated with progression (OR = 5.2, P = 0.012). Kaplan-Meier survival curve showed that patients with STAT5A low expression had worse EFS and OS than those with STAT5A high expression (P < 0.01). Furthermore, the multivariate analysis revealed STAT5A was an independent prognostic factor for poor OS (HR = 3.29, P = 0.0408)) and EFS (HR = 7.29, P = 0.0025). GSEA showed that the complemen, metabolism, apoptosis, interferon-gamma response, inflammatory response, Notch, Kras, reactive oxygen species, VEGF, IL-6/JAK/STAT3, IL-2/Stat5, B-cell receptor, and p53 pathways were significantly associated with the STAT5A gene.
STAT5A may be a novel prognostic factor for osteosarcoma and may act as a molecular target in the treatment of osteosarcoma.
信号转导与转录激活因子5(STAT5)在多种肿瘤的恶性进展中起关键作用,并已被确定为治疗靶点。然而,STAT5A在骨肉瘤中的作用仍不清楚。
从治疗性应用研究以产生有效治疗方法(TARGET)中获取98例骨肉瘤患者。使用Wilcoxon符号秩检验和逻辑回归分析STAT5A与临床特征之间的关系。采用Kaplan-Meier法、单因素和多因素Cox回归分析评估无事件生存期(EFS)和总生存期(OS)的预后价值。进行基因集富集分析(GSEA)。
STAT5A低表达与年龄、性别、肿瘤部位、手术方式、肿瘤区域、组织学反应和转移无关,但与病情进展相关(OR = 5.2,P = 0.012)。Kaplan-Meier生存曲线显示,STAT5A低表达患者的EFS和OS比STAT5A高表达患者更差(P < 0.01)。此外,多因素分析显示STAT5A是OS(HR = 3.29,P = 0.0408)和EFS(HR = 7.29,P = 0.0025)不良的独立预后因素。GSEA显示,补体、代谢、凋亡、干扰素-γ反应、炎症反应、Notch、Kras、活性氧、VEGF、IL-6/JAK/STAT3、IL-2/Stat5、B细胞受体和p53通路与STAT5A基因显著相关。
STAT5A可能是骨肉瘤的一个新的预后因素,并且可能作为骨肉瘤治疗的分子靶点。