采用脑脊液宏基因组二代测序联合拷贝数变异分析技术辅助诊断脑膜癌病

Detection of meningeal carcinomatosis by metagenomic next-generation sequencing and copy number variation analysis of cerebrospinal fluid

目的初步探索通过脑脊液宏基因组二代测序(mNGS)联合染色体拷贝数变异(CNV)分析技术对脑膜癌病辅助诊断的意义。方法连续入组北京协和医院神经科2022年3月至2022年6月确诊的10例脑膜癌病患者。脑膜癌病的诊断依据中华医学会神经病学分会感染性疾病与脑脊液细胞学学组《脑膜癌病诊断专家共识》的标准,经脑脊液细胞学确诊。采用脑脊液mNGS病原微生物与CNV双组学检测。对照组为中枢神经系统炎性疾病患者,包括自身免疫性脑炎与病毒性脑炎,共10例。结果入组的10例脑膜癌病患者中,肿瘤来源包括乳腺癌4例、肺癌6例。脑脊液mNGS联合CNV检测结果8例阳性,检测到非整倍体CNV,支持脑膜癌病的诊断;阳性率为8/10,阳性患者的肿瘤来源包括肺癌4例、乳腺癌4例。脑脊液CNV阴性患者2例,均为肺癌。全部患者脑脊液mNGS病原微生物分析结果均阴性;对照组CNV分析结果无阳性病例。结论脑脊液CNV可作为脑膜癌病的诊断标志物,mNGS联合CNV对诊断脑膜癌病具有较高的阳性率,病原微生物与CNV的双组学联合分析的检测策略有助于拓宽脑脊液mNGS在临床辅助诊断的应用范围。

Objective To evaluate the significance of copy number variation(CNV)and metagenomic next-generation sequencing(mNGS)of cerebrospinal fluid(CSF)in the diagnosis of meningeal carcinomatosis(MC).Methods Ten patients with MC diagnosed in the Department of Neurology of Peking Union Medical College Hospital from March 2022 to June 2022 were consecutively enrolled in this study.The patients were diagnosed according to the criteria of the Chinese expert consensus on the diagnosis of MC by the Chinese Society of Infectious Diseases and Cerebrospinal Fluid Cytology,and the diagnosis of MC was confirmed by CSF cytology.The control group included 10 patients who were diagnosed as autoimmune encephalitis or viral encephalitis.CSF mNGS and CNV analysis were performed simultaneously in all the patients.Results Of the 10 patients with MC,6 had lung adenocarcinoma,4 had breast cancer.CSF mNGS and CNV analysis detected large CNV in 8 of 10 patients with MC,including 4 patients with breast cancer and 4 patients with lung cancer.The results of pathogenic microorganism analysis of CSF mNGS in all the patients were negative.Meanwhile,large CNV was not detected in the control group.Conclusions CSF CNV can serve as a diagnostic marker for MC.The combination of mNGS and CNV analysis has demonstrated a high positive rate in the diagnosis of MC.The dual-omics analysis of pathogenic microorganisms and CNV has been proposed as a potential strategy to further expand the clinical utility of CSF mNGS in the realm of auxiliary diagnosis.