PDF(Pubmed)
Abstract：
Glioblastoma (GBM) continues to exhibit a discouraging survival rate despite extensive research into new treatments. One factor contributing to its poor prognosis is the tumor\'s immunosuppressive microenvironment, in which the kynurenine pathway (KP) plays a significant role. This study aimed to explore how KP impacts the survival of newly diagnosed GBM patients. We examined tissue samples from 108 GBM patients to assess the expression levels of key KP markers-tryptophan 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenase (IDO1/2), and the aryl hydrocarbon receptor (AhR). Using immunohistochemistry and QuPath software, three tumor cores were analyzed per patient to evaluate KP marker expression. Kaplan-Meier survival analysis and stepwise multivariate Cox regression were used to determine the effect of these markers on patient survival. Results showed that patients with high expression of TDO2, IDO1/2, and AhR had significantly shorter survival times. This finding held true even when controlling for other known prognostic variables, with a hazard ratio of 3.393 for IDO1, 2.775 for IDO2, 1.891 for TDO2, and 1.902 for AhR. We suggest that KP markers could serve as useful tools for patient stratification, potentially guiding future immunomodulating trials and personalized treatment approaches for GBM patients.
摘要：
尽管对新疗法进行了广泛的研究，但胶质母细胞瘤（GBM）的存活率仍然令人沮丧。导致其预后不良的一个因素是肿瘤的免疫抑制微环境，其中犬尿氨酸途径(KP)起重要作用。本研究旨在探讨KP如何影响新诊断的GBM患者的生存。我们检查了108例GBM患者的组织样本，以评估关键KP标志物-色氨酸2,3-双加氧酶（TDO2）的表达水平，吲哚胺2,3-双加氧酶（IDO1/2），和芳基烃受体(AhR)。使用免疫组织化学和QuPath软件，对每位患者的3个肿瘤核心进行分析,以评估KP标志物的表达.使用Kaplan-Meier生存分析和逐步多变量Cox回归来确定这些标志物对患者生存的影响。结果显示，TDO2，IDO1/2和AhR高表达的患者的生存时间明显缩短。即使控制其他已知的预后变量，这一发现也是正确的。IDO1的危险比为3.393，IDO2为2.775，TDO2为1.891，AhR为1.902。我们建议KP标志物可以作为患者分层的有用工具，可能指导未来的免疫调节试验和GBM患者的个性化治疗方法。
