目的:多形性胶质母细胞瘤(GBM),一种最常见的原发性恶性颅内脑肿瘤。在印度,这种恶性肿瘤的发病率正在上升,然而,很少有印度人群对这种肿瘤实体的研究。本研究旨在调查印度西部GBM患者中信号转导和转录激活因子3(STAT3)基因表达的患病率和预后意义。
方法:使用实时PCR检测55例GBM患者的STAT3基因表达。使用单变量和多变量生存分析来分析STAT3异常表达对无进展生存(PFS)和总体(OS)的影响。采用SPSS统计软件对数据进行分析,p值≤0.05为显著性。
结果:在85%(47/55)的患者中发现STAT3表达异常,在49%(23/47)的患者中有-1.12倍的变化下调,在51%(24/47)的患者中有3.36倍的变化上调。在野生型IDH肿瘤(n=30)中,在63%和27%的患者中注意到STAT3的下调和上调,分别,然而,对于IDH突变型GBM肿瘤(n=25),在16%和68%的患者中注意到STAT3低表达和高表达的发生率,分别。因此,我们发现,在IDH野生型肿瘤患者中,STAT3下调的发生率显著较高,然而,在IDH突变型GBM肿瘤中,上调STAT3的发生率明显较高(P=0.021,χ2=12.81,r=+0.310)。在Kaplan-Meier单变量生存分析中,年龄的一部分(P=0.006),肿瘤位置(P=0.025),和KPS评分(P=0.002),联合检测STAT3上调和存在IDH突变(P=0.030)仍然是影响PFS和OS的重要预后因素。在多变量生存分析中,联合检测STAT3高表达和存在IDH突变仍然是PFS(HR=6.45,95%CI=1.32-31.40,P=0.021)和OS(HR=8.69,95%CI=1.66-45.51,P=0.010)的独立预测因子。
结论:对于GBM肿瘤,STAT3上调和IDH突变的存在共同预测更好的存活率。这反映了GBM患者的独特分子病因。因此,它们将在未来用于靶向治疗,对于临床医生,它们将有助于更好的患者管理.然而,需要对更大样本量的研究进行验证。
OBJECTIVE: Glioblastoma Multiforme (GBM), a devastating the most common primary malignant intracranial brain tumors. In India, the incidence of this malignancy is escalating, however, there are very few studies on this tumor entity from Indian population. The present
study sought to investigate the prevalence and prognostic significance of Signal Transducer and Activator of Transcription 3 (STAT3) gene expression in GBM patients from Western India.
METHODS: STAT3 gene expression using real-time PCR was detected in total 55 GBM patients. The impact of STAT3 aberrant expression on progression-free survival (PFS) and overall (OS) was analysed using univariate and multivariate survival analysis. The data were analysed using SPSS statistical software and p value ≤0.05 was considered as significant.
RESULTS: The aberrant STAT3 expression was found in 85% (47/55) of patients with -1.12 fold change down-regulation in 49% (23/47) and 3.36 fold change up-regulation was noted in 51% (24/47) of patients. In wild type
IDH tumors (n=30), down regulation and up regulation of STAT3 was noted in 63% and 27% of patients, respectively, whereas, for
IDH mutant GBM tumors (n=25), the incidence of low expression and high expression of STAT3 was noted in 16% and 68% of patients, respectively. Thus, we found that incidence of STAT3 down regulation was significantly high in patients with IDH wild type tumors, whereas, in
IDH mutant GBM tumors, the incidence of up-regulated STAT3 was significantly high (P=0.021, χ2=12.81, r=+0.310). In Kaplan-Meier univariate survival analysis, a part from age (P=0.006), tumor location (P=0.025), and KPS score (P=0.002), co-detection of STAT3 up regulation and presence of IDH mutation (P=0.030) remained significant prognostic factors for PFS and OS. In multivariate survival analysis also, co-detection of STAT3 high expression and presence of IDH mutation remained independent prognosticators for PFS (HR=6.45, 95% CI=1.32-31.40, P=0.021) and OS (HR=8.69, 95% CI=1.66-45.51, P=0.010).
CONCLUSIONS: For GBM tumors, STAT3 up-regulation and presence of IDH mutations together predicts better survival. This reflects unique molecular etiology for GBM patients. Therefore, they would be useful in the future for targeted therapy and for clinicians they would be useful for better patient management. However,
study on a larger sample size is required for validation.