Trudeau Julia, Ng Ding Quan, Sayer Michael, Tan Chia Jie, Ke Yu, Chan Raymond J, Chan Alexandre
Department of Clinical Pharmacy Practice, University of California Irvine, 802 W Peltason Dr, Irvine, CA, 92697-4625, USA.
Department of Pharmacotherapy, University of Utah, Salt Lake City, UT, USA.
BMC Cancer. 2025 Jul 1;25(1):1045. doi: 10.1186/s12885-025-14430-3.
Inflammatory signaling is linked with cancer-related cognitive impairment (CRCI), potentially through modulation of brain-derived neurotrophic factor (BDNF) expression. Here, we evaluate associations between plasma cytokines and BDNF and their relationship with cognition in a longitudinal study of adolescent and young adult cancer patients (AYAC) receiving chemotherapy and non-cancer controls (NC) (Clinicaltrials.gov: NCT03476070).
Newly diagnosed AYAC (15-39 years old) and age-matched NC completed the Functional Assessment of Cancer Therapy-Cognitive Function questionnaire (FACT-Cog), the Cambridge Neuropsychological Test Automated Battery (CANTAB), and blood draws every 3-6 months up to 12 months (AYAC) or 6 months (NC) from baseline. Plasma levels of cytokines and BDNF were quantified using a multiplexed immunoassay and ELISA, respectively. Biomarker-cognition and cytokine-BDNF associations were analyzed using mixed-effects models with interactions for chemotherapy status for AYAC (during chemotherapy vs. > 30 days post-chemotherapy).
One-hundred and seventy-seven participants were included, with 66 AYAC and 111 NC. AYAC had a higher frequency of clinically significant cognitive impairment during and post-chemotherapy compared to NC. In trends unique to AYAC, higher IL-10 was associated with better self-perceived cognition, IL-8 with better multi-tasking, IL-6 with worse multi-tasking, response speed, and attention, and TNF-α with better memory (p < 0.05). Higher BDNF was associated with better memory and response speed (p < 0.05). IL-4, IL-10, TNF-α, and IFN-γ were associated with BDNF levels among AYAC and NC (p < 0.05).
Our large, age-matched study implicates dysregulated cytokine signaling and altered BDNF expression in CRCI among AYAC during and post-chemotherapy. As precision medicine becomes integrated into AYA patient care, plasma BDNF and cytokines may serve as important predictors of CRCI onset.
The study was prospectively registered on ClinicalTrials.gov (NCT03476070) on March 3, 2018.
炎症信号通路与癌症相关认知障碍（CRCI）有关，可能是通过调节脑源性神经营养因子（BDNF）的表达来实现的。在此，我们在一项针对接受化疗的青少年和年轻成年癌症患者（AYAC）及非癌症对照者（NC）的纵向研究中（Clinicaltrials.gov：NCT03476070），评估血浆细胞因子与BDNF之间的关联及其与认知的关系。
新诊断的AYAC（15 - 39岁）和年龄匹配的NC完成癌症治疗认知功能问卷（FACT - Cog）、剑桥神经心理测试自动成套系统（CANTAB），并从基线开始每3 - 6个月进行一次血液采集，AYAC为期12个月，NC为期6个月。分别使用多重免疫测定法和酶联免疫吸附测定法（ELISA）对血浆细胞因子和BDNF水平进行定量。使用混合效应模型分析生物标志物与认知以及细胞因子与BDNF之间的关联，并对AYAC的化疗状态（化疗期间与化疗后> 30天）进行交互分析。
共纳入177名参与者，其中66名AYAC和111名NC。与NC相比，AYAC在化疗期间及化疗后出现临床显著认知障碍的频率更高。在AYAC特有的趋势中，较高的白细胞介素-10（IL - 10）与更好的自我认知相关，白细胞介素-8（IL - 8）与更好的多任务处理能力相关，白细胞介素-6（IL - 6）与更差的多任务处理能力、反应速度及注意力相关，肿瘤坏死因子-α（TNF - α）与更好的记忆力相关（p < 0.05）。较高的BDNF与更好的记忆力和反应速度相关（p < 0.05）。在AYAC和NC中，白细胞介素-4（IL - 4）、白细胞介素-10、肿瘤坏死因子-α和干扰素-γ（IFN - γ）与BDNF水平相关（p < 0.05）。
我们这项大规模、年龄匹配的研究表明，在AYAC化疗期间及化疗后，CRCI中存在细胞因子信号失调和BDNF表达改变。随着精准医学融入AYA患者护理中，血浆BDNF和细胞因子可能成为CRCI发病的重要预测指标。
该研究于2018年3月3日在ClinicalTrials.gov（NCT03476070）上进行了前瞻性注册。
