Cerebrospinal fluid metabolomic profiles can discriminate patients with leptomeningeal carcinomatosis from patients at high risk for leptomeningeal metastasis

Abstract

Purpose: Early diagnosis of leptomeningeal carcinomatosis (LMC) is necessary to improve outcomes of this formidable disease. However, cerebrospinal fluid (CSF) cytology is frequently false negative. We examined whether CSF metabolome profiles can be used to differentiate patients with LMC from patients having a risk for development of LMC.Results: A total of 10,905 LMIs were evaluated using PCA-DA. The LMIs defined Group 2 with a sensitivity of 85% and a specificity of 91%. After selecting 33 LMIs, including diacetylspermine and fibrinogen fragments, the CSF metabolomics profile had a sensitivity of 100% and a specificity of 93% for discriminating Group 1b from the other groups. After selecting 21 LMIs, including phosphatidylcholine, the CSF metabolomics profile differentiated LMC (Group 2) patients from the high-risk groups of Group 3 and Group 4 with 100% sensitivity and 100% specificity. Materials and Methods: We prospectively collected CSF from five groups of patients: Group 1a, systemic cancer; Group 1b, no tumor; Group 2, LMC; Group 3, brain metastasis; Group 4, brain tumor other than brain metastasis. All metabolites in the CSF samples were detected as low-mass ions (LMIs) using mass spectrometry. Principal component analysis-based discriminant analysis (PCA-DA) and two search algorithms were used to select the LMIs that differentiated the patient groups of interest from controls.Conclusions: Analysis of CSF metabolite profiles could be used to diagnose LMC and exclude patients at high-risk of LMC with a 100% accuracy. We expect a future validation trial to evaluate CSF metabolic profiles supporting CSF cytology.

Analysis of cerebrospinal fluid metabolites in patients with primary or metastatic central nervous system tumors

“…To our knowledge, this study is one of the most comprehensive analysis of CSF metabolites in patients with different types of primary or metastatic CNS tumors [ 12 , 16 , 23 ]. Our results show that it is possible to discriminate CSF from patients with IDH-mutant or IDH-WT gliomas and metastatic carcinomas, from patients with non-neoplastic conditions.…”

Experimental Assessment of Leptomeningeal Metastasis Diagnosis in Medulloblastoma Using Cerebrospinal Fluid Metabolomic Profiles

“…CSF metabolites were extracted using a modified Bligh and Dyer method, as previously described [15]. Briefly, 50 µL CSF was added to 1 mL water, 2 mL methanol, and 0.9 mL dichloromethane, and mixed thoroughly by vortexing.…”

“…Advances in high-resolution mass spectrometry (MS) techniques have enabled the identification of small concentrations of metabolites in biofluids of cancer patients [14]. Previously, we elucidated discriminative metabolomic profiles according to varying CNS tumor statuses including LM from solid primary cancers in CSF of 196 patients [15].…”

Resolving Metabolic Heterogeneity in Experimental Models of the Tumor Microenvironment from a Stable Isotope Resolved Metabolomics Perspective

“…Metabolic profiling of tissues and biofluids including blood plasma [80][81][82][83], urine [84][85][86], and cerebrospinal fluid (CSF) [86][87][88][89] using NMR and MS in the past decade has been shown to be very valuable for reporting disease states and drug responses. This is due to metabolic reprogramming in • C/5% CO 2 before fixing in 4% buffered formalin, embedded in paraffin block, and sectioned into 4 µm slices for H&E staining in (A) and IF staining for cancer cells (panCytokeratin or panCK), CD8 (cytotoxic T cells), and CD68 (Mφ) in (B).…”