鞘内合成的肿瘤标志物与血脑屏障完整性在肺癌软脑膜转移诊断中的价值  

Diagnostic Value of Locally Produced Tumor Markers and Blood Brain Barrier Integrity in Lung Cancer Patients with Leptomeningeal Metastasis

作　　者：林永娟[1] 俞婷婷[1] 李会颖 尹震宇[1] 郭爱斌[1] Yongjuan LIN;Tingting YU;Huiying LI;Zhenyu YIN;Aibin GUO(Department of Geriatric Oncology,Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院老年肿瘤科,南京210008

出　　处：《中国肺癌杂志》2021年第8期567-576,共10页Chinese Journal of Lung Cancer

基　　金：南京市卫生局重点项目(No.ZKX16031);南京市科学技术委员会医疗卫生项目(No.201715020);南京市医学重点科技发展项目(No.ZKX18014);希思科-豪森肿瘤研究基金(No.Y-HS2019-5)资助。

摘　　要：背景与目的脑脊液(cerebrospinal fluid,CSF)中肿瘤标志物(tumor markers,TM)对软脑膜转移(leptomeningeal metastasis,LM)具有诊断意义,但因TM在CSF中浓度很大程度上取决于血清水平以及血脑屏障(blood brain barrier,BBB)的状态,因此,CSF中TM诊断LM的价值常常被忽视。明确鞘内TM合成、BBB的完整性可为LM临床诊断提供帮助。因此,本研究从BBB完整性和鞘内TM合成角度出发,进一步探讨CSF中TM对肺癌LM诊断的临床价值。方法收集2016年12月-2020年3月于南京鼓楼医院治疗的肺癌伴LM的患者25例,另选本院同期治疗的57例非恶性神经系统疾病(nonmalignant neurological diseases,NMNDs)患者为对照组,分析比较BBB完整性和鞘内TM合成的差异,评估LM组CSF中TM检出阳性率与鞘内TM合成的相关性,并动态监测1例LM患者脑室内化疗过程中CSF细胞学、BBB完整性以及鞘内TM合成的变化。结果LM患者中94%存在BBB破坏。所有LM患者CSF中至少存在一项TM的鞘内合成,其中1例患者,首次CSF细胞学阴性,但是存在鞘内TM合成,重复腰穿CSF细胞学阳性确诊为LM。LM组CSF中TM检出阳性率与TM鞘内合成不一致。对照组中仅3.5%(2/57)NMNDs患者有BBB破坏,且未在鞘内合成TM,差异有统计学意义(P<0.05)。另外,动态监测CSF细胞学、BBB完整性和CSF鞘内合成的TM与疗效评价一致,且鞘内TM合成的变化早于细胞学。结论BBB的评估及鞘内TM合成的分析可为LM患者提供一个早期辅助诊断的工具,动态监测TM可能有助于疗效评估,值得临床推广应用。Background and objective Tumor markers(TM)in cerebrospinal fluid(CSF)are useful for diagnosing leptomeningeal metastasis(LM).It has not been fully exploited the diagnostic possibilities of the CSF levels since the basic fact that the TM concentration of CSF depends strongly upon the serum levels as well as upon the condition of the blood brain barrier(BBB).To analyze the intrathecal TM synthesis and evaluate the integrity of BBB can be helpful for the definitive diagnosis of LM.Therefore,the aim of this study was to further explore the clinical value of intrathecal TM synthesis and BBB in the diagnosis for the lung cancer patients with LM.Methods Twenty-five lung cancer patients with LM and 57 patients with nonmalignant neurological diseases(NMNDs)admitted to Nanjing Drum Tower Hospital from December 2016 to March 2020 were included.We compared the integrity of BBB and intrathecal TM synthesis between two groups,analyzed the correlation of CSF TM between the detection and intrathecal synthesis,and evaluated serial CSF cytology,the integrity of BBB and intrathecal TM synthesis when intrathecal chemotherapy for one patient.Results Ninety-four percent LM patients showed the dysfunction of BBB,and all LM patients showed at least one intrathecal synthesized TM in CSF.In one patient,the CSF cytology was negative for the first time,but LM was eventually diagnosed based on the the intrathecal TM synthesis and positive CSF cytology of repeated lumbar puncture.In LM group,no correlation was observed between the detection and intrathecal synthesized TM in CSF.In the control group,only 3.5%(2/57)NMNDs patients had the dysfunction of BBB and no patients had intrathecal TM synthesis,both the differences of which were statistically significant(P<0.05).Finally,evaluating the CSF cytology,integrity of BBB and intrathecal TM synthesis can be used to assess the intracranial treatment effect.Moreover,intrathecal TM synthesis changes earlier than cytology.Conclusion The evaluation of intrathecal TM synthesis and integrity of BBB are

关 键 词：肺肿瘤 软脑膜转移 脑脊液 肿瘤标志物 鞘内合成 血脑屏障 

分 类 号：R734.2[医药卫生—肿瘤]