Medulloblastoma cerebrospinal fluid reveals hypoxic indicators (metabolites and lipids) and cancer-specific RNAs. Medulloblastoma cerebrospinal fluid reveals hypoxic indicators (metabolites and lipids) and cancer-specific RNAs

Medulloblastoma (MB) is the most common malignant brain tumor in children. There remains an unmet need for diagnostics to sensitively detect the disease, particularly recurrences. Cerebrospinal fluid (CSF) provides a window into the central nervous system, and liquid biopsy of CSF could provide a relatively non-invasive means for disease diagnosis. CSF samples from patients with or without medulloblastoma (MB) were subjected to RNA-sequencing to identify differentially expressed transcripts. Although the transcriptomic signatures in CSF to differentiate MB subgroup separation was challenging, we were able to identify a group of gene signatures that could separate cancer from normal CSF. Our approach provides several candidate signatures that deserve further validation, including the novel circular RNA circ_463, and insights into the impact of MB on the CSF microenvironment. Overall design: CSF samples from patients with (n=40) or without (n=11; no cancer) MB were subjected to RNA-sequencing. RNAs were purified from 0.2 mL CSF and library was made Ovation SoLo system (NuGen). Libraries were subjected to RNA-sequencing using a NextSeq550 (illumina).

髓母细胞瘤（Medulloblastoma, MB）是儿童最常见的恶性脑肿瘤。目前仍存在未被满足的诊断需求，亟需开发可灵敏检测该病（尤其是其复发情况）的诊断方案。脑脊液（Cerebrospinal fluid, CSF）是窥探中枢神经系统的窗口，脑脊液液体活检可为疾病诊断提供相对无创的途径。本研究收集了伴或不伴髓母细胞瘤（MB）患者的脑脊液样本，通过RNA测序筛选差异表达转录本。尽管通过脑脊液转录组特征区分MB亚型颇具挑战，但本研究成功鉴定出一组可区分癌性与正常脑脊液的基因特征，其中包含多个值得进一步验证的候选特征（包括新型环状RNA circ_463），同时为解析髓母细胞瘤对脑脊液微环境的影响提供了新的认知。整体实验设计如下：收集伴MB患者（n=40）与无MB（n=11，无癌症）患者的脑脊液样本；从0.2 mL脑脊液中纯化RNA，使用Ovation SoLo系统（NuGen公司）构建测序文库；随后采用NextSeq550（Illumina公司）测序平台完成RNA测序。