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

Journal: Clinica chimica acta; international journal of clinical chemistry
Published Date: May 19, 2025

Abstract

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.

Authors

  • Jingjing Ma
    Department of Geriatrics, Renmin Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, 430060, China.
  • Di Wang
    Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing, People's Republic of China.
  • Xiangyu Li
  • Yaqi Zhang
    Key Laboratory of Symbolic Computation and Knowledge Engineering of Ministry of Education, Jilin University, Changchun, Jilin, 130012, China; College of Computer Science and Technology, Jilin University, Changchun, Jilin, 130012, China.
  • Qiming Tang
    mProbe Inc., Palo Alto, CA 94303, USA. Electronic address: qiming.tang@mprobe.com.
  • Yun Ding
    Office of Chairman, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, 215028, China. 70586655@qq.com.
  • Xiao Li
    Department of Inner Mongolia Clinical Medicine College, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.
  • Bo Jin
    HBISolutions Inc., Palo Alto, CA 94301, USA.
  • Ruben Y Luo
    Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: rubenluo@stanford.edu.
  • Sheeno Thyparambil
    mProbe Inc., Palo Alto, CA 94303, USA. Electronic address: sheeno@mprobe.com.
  • Zhi Han
    School of Microelectronics, Southeast University, Wuxi 214135, China. 220153639@seu.edu.cn.
  • C James Chou
    Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: cjchou@stanford.edu.
  • Ashlee Zhou
    mProbe Inc., Palo Alto, CA 94303, USA. Electronic address: ashleezhou12@gmail.com.
  • James Schilling
    mProbe Inc., Palo Alto, CA 94303, USA. Electronic address: james.s@mprobe.com.
  • Zhiguang Lin
    Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Yan Ma
    Medical School of Chinese PLA, 100853 Beijing, China.
  • Qing Li
    Department of Internal Medicine, University of Michigan Ann Arbor, MI 48109, USA.
  • Mengxue Zhang
    Chimie ParisTech, PSL University Paris, CNRS, Institut de Recherche de Chimie Paris, UMR8247, 11 rue Pierre et Marie Curie, Paris, 75005, France.
  • Karl G Sylvester
    Departments of Surgery, Stanford University, Stanford, CA 94305, USA.
  • Seema Nagpal
    Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: snagpal@stanford.edu.
  • Doff B McElhinney
    Stanford University, Stanford, California, United States of America.
  • Xuefeng B Ling
    Departments of Surgery, Stanford University, Stanford, CA 94305, USA. Electronic address: bxling@stanford.edu.
  • Bobin Chen
    Department of Hematology, Huashan Hospital, Fudan University, Shanghai 200040, China.

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