Cerebrospinal fluid metabolic markers predict prognosis behavior of primary central nervous system lymphoma with high-dose methotrexate-based chemotherapeutic treatment

Author:

Zhou Liying1,Li Qing2,Xu Jingshen1,Wang Shuaikang1,Song Zhiqiang13,Chen Xinyi1,Ma Yan2,Lin Zhiguang2,Chen Bobin2,Huang He14ORCID

Affiliation:

1. Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University , Shanghai, 200438 , China

2. Department of Hematology, Huashan Hospital, Fudan University , Shanghai, 200438 , China

3. School of Life Sciences, Inner Mongolia University , Hohhot Inner Mongolia, 010021 , China

4. Shanghai Qi Zhi Institute , Shanghai, 200030 , China

Abstract

AbstractBackgroundPrimary central nervous system lymphoma (PCNSL) is a highly aggressive non-Hodgkin’s B-cell lymphoma which normally treated by high-dose methotrexate (HD-MTX)-based chemotherapy. However, such treatment cannot always guarantee a good prognosis (GP) outcome while suffering several side effects. Thus, biomarkers or biomarker-based models that can predict PCNSL patient prognosis would be beneficial.MethodsWe first collected 48 patients with PCNSL and applied HPLC-MS/MS-based metabolomic analysis on such retrospective PCNSL patient samples. We then selected the highly dysregulated metabolites to build a logical regression model that can distinguish the survival time length by a scoring standard. Finally, we validated the logical regression model on a 33-patient prospective PCNSL cohort.ResultsSix metabolic features were selected from the cerebrospinal fluid (CSF) that can form a logical regression model to distinguish the patients with relatively GP (Z score ≤0.06) from the discovery cohort. We applied the metabolic marker-based model to a prospective recruited PCNSL patient cohort for further validation, and the model preformed nicely on such a validation cohort (AUC = 0.745).ConclusionsWe developed a logical regression model based on metabolic markers in CSF that can effectively predict PCNSL patient prognosis before the HD-MTX-based chemotherapy treatments.

Funder

National Key R&D Program of China

Natural Science Foundation of China

Shanghai Sailing Program

Shanghai Shenkang clinical science and technology innovation project

Publisher

Oxford University Press (OUP)

Subject

Surgery,Oncology,Neurology (clinical)

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