Abou-Ghazal Mohamed, Yang David S, Qiao Wei, Reina-Ortiz Chantal, Wei Jun, Kong Ling-Yuan, Fuller Gregory N, Hiraoka Nobuyoshi, Priebe Waldemar, Sawaya Raymond, Heimberger Amy B
Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Clin Cancer Res. 2008 Dec 15;14(24):8228-35. doi: 10.1158/1078-0432.CCR-08-1329.
The signal transducer and activator of transcription 3 (STAT3) is frequently overexpressed in most cancers, propagates tumorigenesis, and is a key regulator of immune suppression in cancer patients. We sought to determine the incidence of phosphorylated STAT3 (p-STAT3) expression in malignant gliomas of different pathologic types, whether p-STAT3 expression is a negative prognostic factor, and whether p-STAT3 expression influences the inflammatory response within gliomas.
Using immunohistochemical analysis, we measured the incidence of p-STAT3 expression in 129 patients with gliomas of various pathologic types in a glioma tissue microarray. We categorized our results according to the total number of p-STAT3-expressing cells within the gliomas and correlated this number with the number of infiltrating T cells and T regulatory cells. We then evaluated the association between p-STAT3 expression and median survival time using univariate and multivariate analyses.
We did not detect p-STAT3 expression in normal brain tissues or low-grade astrocytomas. We observed significant differences in the incidence of p-STAT3 expression between the different grades of astrocytomas and different pathologic glioma types. p-STAT3 expression was associated with the population of tumor-infiltrating immune cells but not with that of T regulatory cells. On univariate analysis, we found that p-STAT3 expression within anaplastic astrocytomas was a negative prognostic factor.
p-STAT3 expression is common within gliomas of both the astrocytic and oligodendroglial lineages and portends poor survival in patients with anaplastic astrocytomas. p-STAT3 expression differs significantly between gliomas of different pathologic types and grades and correlated with the degree of immune infiltration.
信号转导与转录激活因子3（STAT3）在大多数癌症中经常过度表达，促进肿瘤发生，并且是癌症患者免疫抑制的关键调节因子。我们试图确定不同病理类型的恶性胶质瘤中磷酸化STAT3（p-STAT3）表达的发生率，p-STAT3表达是否为阴性预后因素，以及p-STAT3表达是否影响胶质瘤内的炎症反应。
使用免疫组织化学分析，我们在胶质瘤组织芯片中测量了129例不同病理类型胶质瘤患者中p-STAT3表达的发生率。我们根据胶质瘤内表达p-STAT3的细胞总数对结果进行分类，并将该数量与浸润性T细胞和调节性T细胞的数量相关联。然后，我们使用单因素和多因素分析评估p-STAT3表达与中位生存时间之间的关联。
我们在正常脑组织或低级别星形细胞瘤中未检测到p-STAT3表达。我们观察到不同级别的星形细胞瘤和不同病理类型的胶质瘤之间p-STAT3表达的发生率存在显著差异。p-STAT3表达与肿瘤浸润免疫细胞群体相关，但与调节性T细胞群体无关。在单因素分析中，我们发现间变性星形细胞瘤内的p-STAT3表达是一个阴性预后因素。
p-STAT3表达在星形细胞和少突胶质细胞系的胶质瘤中很常见，并且预示着间变性星形细胞瘤患者的生存不良。p-STAT3表达在不同病理类型和级别的胶质瘤之间存在显著差异，并且与免疫浸润程度相关。
