Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4A, 18 Science Drive 4, Level 3, Singapore, 117543, Singapore.
Department of Pharmacy, National Cancer Centre Singapore, Singapore, Singapore.
BMC Cancer. 2017 Dec 19;17(1):867. doi: 10.1186/s12885-017-3861-9.
Preliminary evidence suggests that changes in plasma brain-derived neurotrophic factor (BDNF) levels may contribute to the occurrence of chemotherapy-associated cognitive impairment (CACI), and a previous study suggested that carriers of the BDNF Met homozygous genotype are protected from CACI.
This multicenter, prospective cohort study involved chemotherapy-receiving early-stage breast cancer (ESBC) patients. Self-perceived cognitive function was longitudinally assessed using the validated FACT-Cog (ver. 3) across three time points: Prior to chemotherapy (T1), during chemotherapy (T2), and at the end of chemotherapy (T3). Plasma BDNF levels were quantified using enzyme-linked immunosorbent assay. Genotyping was performed using Sanger Sequencing.
A total of 51 chemotherapy-receiving ESBC patients (mean age: 52.6 ± 9.5 years) were recruited, and 11 patients (21.6%) reported subjective cognitive impairment post-chemotherapy. Overall, there was a reduction in median plasma BDNF levels over time (T1: 5423.0 pg/ml; T2: 5313.6 pg/ml; T3: 4050.3 pg/ml; p < 0.01). After adjusting for confounding factors, longitudinal analysis revealed that BDNF levels were associated with self-reported concentration deficit (p = 0.032). Carriers of Val/Val (p = 0.011) and Val/Met (p = 0.003) BDNF genotypes demonstrated a significant reduction in plasma BDNF levels over time; however, plasma BDNF levels were similar across all time points among Met homozygous carriers (p = 0.107).
There was a statistically significant change in BDNF levels post-chemotherapy in ESBC patients, and plasma BDNF levels were associated with self-perceived concentration deficit in patients receiving chemotherapy.
初步证据表明，血浆脑源性神经营养因子（BDNF）水平的变化可能与化疗相关认知障碍（CACI）的发生有关，先前的研究表明，BDNF Met 纯合基因型携带者可免受 CACI 的影响。
这是一项多中心、前瞻性队列研究，纳入了接受化疗的早期乳腺癌（ESBC）患者。使用经过验证的 FACT-Cog（版本 3）在三个时间点（化疗前（T1）、化疗期间（T2）和化疗结束时（T3））进行纵向评估自我感知的认知功能。使用酶联免疫吸附测定法定量测定血浆 BDNF 水平。使用 Sanger 测序进行基因分型。
共招募了 51 名接受化疗的 ESBC 患者（平均年龄：52.6±9.5 岁），11 名患者（21.6%）在化疗后报告有主观认知障碍。总的来说，随着时间的推移，中位血浆 BDNF 水平呈下降趋势（T1：5423.0 pg/ml；T2：5313.6 pg/ml；T3：4050.3 pg/ml；p<0.01）。调整混杂因素后，纵向分析显示 BDNF 水平与自我报告的注意力缺陷有关（p=0.032）。Val/Val（p=0.011）和 Val/Met（p=0.003）BDNF 基因型携带者的 BDNF 水平随时间显著降低；然而，在所有时间点，Met 纯合型携带者的血浆 BDNF 水平相似（p=0.107）。
ESBC 患者化疗后 BDNF 水平有统计学意义的变化，接受化疗的患者血浆 BDNF 水平与自我感知的注意力缺陷有关。
