Metabolic pathway alterations in cerebrospinal fluid as diagnostic biomarkers for primary central nervous system lymphoma.

Primary Central Nervous System Lymphoma (PCNSL) is a rare and aggressive type of hematological malignancy that can pose diagnostic challenges. Early detection is critical for effective treatment and better patient outcomes. The goal of this study was to assess the potential of metabolic pathway alterations as diagnostic and differential biomarker. We conducted a metabolomics analysis from GEO transcriptomic datasets on brain/lymph nodes. Enriched and significant pathways were validated from patient's CSF samples from PCNSL, metastatic cancers and non-malignant controls, with mass spectrometry. Next, we utilized machine learning models to assess the separation performance of PCNSLs from other patients and develop diagnostic and differential diagnosis panels. Key metabolic pathways were discovered from GEO datasets analysis and significantly enriched in the CSF of PCNSL. Porphyrin metabolism and fatty acid-related pathways were significantly enriched from diagnostic panel and AUC was 0.88. Additionally, aminoacyl-tRNA biosynthesis, glutathione metabolism, and several amino acid pathways were significantly enriched from differential panel and the AUC was 0.95. Our study highlights the diagnostic biomarker potential of metabolic pathway alterations in CSF for PCNSL, which could lead to the development of non-invasive and reliable diagnostic tool for PCNSL.