解放军医学杂志2024，Vol.49Issue(11)：1281-1288,8.DOI:10.11855/j.issn.0577-7402.0232.2024.1011
趋化因子配体9对乳腺癌脑转移全脑放射治疗患者认知功能衰退的影响
Effect of chemokine CXC ligand 9 on cognitive function impairment in breast cancer patients with brain metastases receiving whole-brain radiotherapy
摘要
Abstract
Objective To investigate the effect of chemokine CXC ligand 9(CXCL9)on cognitive function impairment in patients with breast cancer brain metastases undergoing whole-brain radiotherapy(WBRT)using bioinformatics methods.Methods The mRNA of breast cancer brain metastases datasets GSE43837 and GSE12276 and Alzheimer's disease(AD)dataset GSE161199 were screened and downloaded from GEO database.Limma method and Venn diagrams were used to identify common differentially expressed genes(DEGs),and protein-protein interaction and functional prediction through GeneMANIA website assays were performed.A total of 42 patients with breast cancer brain metastases who first visited the Department of Radiotherapy at the First Affiliated Hospital of Hebei North University from January 2021 to January 2023 were selected.Patients were divided into normal cognitive function group and cognitive function impairment group based on cognitive status.Enzyme-linked immunosorbent assay(ELISA)was employed to detect serum CXCL9 levels one week before and three months after radiotherapy.The mini-mental state examination(MMSE)was used to assess patients'cognitive function.Results The DEGs from datasets GSE43837 and GSE12276 included PKP1,POLDIP2,SPAG5,ALDOC,PTPRZ1,PKIA,TLCD1,CPE,PMP22 and CXCL9.The DEGs from GSE161199 included RPS16,CD79A,LYPD3,RPL28,HBG2,RPL23AP7,TRNR,CXCL9.Venn diagram showed that CXCL9 was a common DEG between breast cancer brain metastasis and AD.Functional enrichment analysis indicated that CXCL9 was involved in cellular responses to chemokines,negative regulation of immune system processes,negative regulation of vascular morphogenesis,Toll-like receptor signaling pathway,nucleotide oligomerization domain(NOD)-like receptor signaling pathway,and JAK-STAT signaling pathway.Before radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 61.9%and 38.1%,respectively,with a statistically significant difference in MMSE scores[(24.53±2.19)vs.(28.89±1.36),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had a significantly increased number of brain metastases and significantly lower Karnofsky performance status(KPS)scores and serum CXCL9 levels(P＜0.05).Three months after radiotherapy,patients with cognitive function impairment and normal cognitive function accounted for 47.6%and 52.4%,respectively,with a statistically significant difference in MMSE scores[(25.16±1.98)vs.(28.18±1.08),P＜0.01].Compared with normal cognitive function group,patients with cognitive function impairment had significantly lower CXCL9 levels(P=0.003).In patients with normal cognitive function,CXCL9 levels were remarkably lower after radiotherapy compared to those before radiotherapy(P=0.009).Conclusions Patients with cognitive function impairment had significantly lower CXCL9 levels than those with normal cognitive function,and whole-brain radiotherapy may be related to a certain degree of reduction in CXCL9 levels.关键词
乳腺癌脑转移/全脑放射治疗/容积调强技术/趋化因子配体9/简易精神状态检查量表Key words
breast cancer brain metastases/whole-brain radiotherapy/volumetric modulated arc therapy/chemokine CXC ligand 9/mini-mental state examination分类
医药卫生引用本文复制引用
王聪,张志林,李锦秋,宋晓,席强,马欢,庞永鹏,田龙..趋化因子配体9对乳腺癌脑转移全脑放射治疗患者认知功能衰退的影响[J].解放军医学杂志,2024,49(11):1281-1288,8.基金项目
This work was supported by the Medical Science Research Project in Hebei Province(20220595) 河北省医学科学研究课题(20220595) （20220595）
