Molecular Diagnostics & Research Laboratory I, The Gujarat Cancer & Research Institute, Ahmedabad, Gujarat, India.
Molecular Diagnostics & Research Lab-I, Cancer Biology Department, Gujarat Cancer & Research Institute, Asarwa, Ahmedabad, Gujarat, 380 016, India.
J Egypt Natl Canc Inst. 2022 Jul 18;34(1):30. doi: 10.1186/s43046-022-00133-4.
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.
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.
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).
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.
多形性胶质母细胞瘤（GBM）是最常见的原发性颅内恶性脑肿瘤。在印度，这种恶性肿瘤的发病率正在上升，但来自印度人群的关于这种肿瘤实体的研究很少。本研究旨在探讨信号转导和转录激活因子 3（STAT3）基因在印度西部 GBM 患者中的表达与预后的相关性。
使用实时 PCR 检测了 55 名 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期（PFS）和总生存期（OS）的影响。数据使用 SPSS 统计软件进行分析，p 值≤0.05 被认为具有统计学意义。
在 85%（47/55）的患者中发现了异常的 STAT3 表达，在 49%（23/47）的患者中存在 -1.12 倍的下调，在 51%（24/47）的患者中存在 3.36 倍的上调。在野生型 IDH 肿瘤（n=30）中，STAT3 的下调和上调分别在 63%和 27%的患者中观察到，而在 IDH 突变型 GBM 肿瘤（n=25）中，STAT3 的低表达和高表达分别在 16%和 68%的患者中观察到。因此，我们发现 IDH 野生型肿瘤患者中 STAT3 下调的发生率明显较高，而 IDH 突变型 GBM 肿瘤患者中 STAT3 上调的发生率明显较高（P=0.021，χ2=12.81，r=+0.310）。在 Kaplan-Meier 单变量生存分析中，除了年龄（P=0.006）、肿瘤位置（P=0.025）和 KPS 评分（P=0.002）外，STAT3 上调的共检测和 IDH 突变的存在（P=0.030）仍然是 PFS 和 OS 的显著预后因素。在多变量生存分析中，STAT3 高表达和 IDH 突变的共检测仍然是 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）的独立预后因素。
对于 GBM 肿瘤，STAT3 的上调和 IDH 突变的存在共同预测更好的生存。这反映了 GBM 患者独特的分子病因。因此，它们将来在靶向治疗中很有用，对临床医生来说，它们对更好的患者管理很有用。但是，需要更大的样本量进行验证。
