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Abstract：
The objective of this study was to assess the prognostic relevance of Stanniocalcin-2 (STC2) expression, as determined via immunohistochemistry in tumor tissue, in a cohort of 83 patients diagnosed with glioblastoma who underwent maximal safe surgical resection followed by radiotherapy concurrent with adjuvant temozolomide. STC2 expression levels were categorized using a 3-tiered semiquantitative system: negative expression (level 0-), low expression (level 1+), and high expression (levels 2 + and 3+). Patients were categorized into 2 distinct groups according to their STC2 expression levels: negative STC2 (-/+) and positive STC2 (++/+++). The primary outcome measure was the relationship between STC2 expression and progression-free survival (PFS), with overall survival (OS) serving as the secondary endpoint. Kaplan-Meier survival analysis confirmed that patients exhibiting high STC2 expression had significantly shorter OS (8 vs 20 months, P < .001) and PFS (6 vs 18 months, P < .001) than those with low or negative STC2 expression. Multivariate analysis revealed that STC2 expression was an independent prognostic factor for both OS (hazard ratio: 0.4; 95% confidence interval: 0.2-0.8; P < .05) and PFS (hazard ratio: 0.3; 95% confidence interval: 0.2-0.4; P < .05) in patients with glioblastoma. Furthermore, elevated STC2 expression in GBM was correlated with several established aggressive clinicopathological characteristics, including advanced age (≥65 years), low ECOG PS (≥2), and isocitrate dehydrogenase mutation negativity. These findings underscore that heightened STC2 expression within the tumor tissue of GBM patients functions as an adverse prognostic marker, correlating with an elevated risk of progression and reduced OS. Therapeutic interventions targeting the AKT-mTOR, ERK1-2, and mitogen-activated protein kinase pathways as well as immune checkpoint inhibitors and vascular endothelial growth factor blockade, as well as potential forthcoming antibody-drug conjugates targeting the STC2 molecule, have the potential to broaden the scope of combined treatment strategies.
摘要：
本研究的目的是评估Stiniocalcin-2（STC2）表达的预后相关性，通过肿瘤组织中的免疫组织化学确定，在一个由83例诊断为胶质母细胞瘤的患者组成的队列中，这些患者接受了最大安全的手术切除，然后进行放疗并辅以替莫唑胺。使用3层半定量系统对STC2表达水平进行分类:阴性表达(水平0-),低表达（1+级），和高表达（水平2+和3+）。根据其STC2表达水平将患者分为2个不同的组:阴性STC2(-/+)和阳性STC2(++/+++)。主要结局指标是STC2表达与无进展生存期（PFS）之间的关系，以总生存期(OS)为次要终点。Kaplan-Meier生存分析证实，STC2高表达患者的OS明显较短（8vs20个月，P<.001）和PFS（6个月vs18个月，P<.001）比STC2表达低或阴性的那些。多因素分析显示，STC2表达是胶质母细胞瘤患者OS（风险比：0.4；95％置信区间：0.2-0.8；P<.05）和PFS（风险比：0.3；95％置信区间：0.2-0.4；P<.05）的独立预后因素。此外，GBM中STC2表达升高与几个已确立的侵袭性临床病理特征相关，包括高龄（≥65岁），低ECOGPS（≥2），和异柠檬酸脱氢酶突变阴性。这些发现强调了GBM患者肿瘤组织中STC2表达的增加作为不良预后标志物。与进展风险升高和OS降低相关。针对AKT-mTOR的治疗性干预措施，ERK1-2和丝裂原激活的蛋白激酶通路以及免疫检查点抑制剂和血管内皮生长因子阻断，以及靶向STC2分子的潜在即将到来的抗体-药物缀合物，有可能扩大联合治疗策略的范围。
