Proteomic profiling of cerebrospinal fluid reveals TKT as a potential biomarker for medulloblastoma

Joo Whan Kim; Seung Ah Choi; Kisoon Dan; Eun Jung Koh; Saehim Ha; Ji Hoon Phi; Kyung Hyun Kim; Dohyun Han; Seung-Ki Kim

doi:10.1038/s41598-024-71738-z

Proteomic profiling of cerebrospinal fluid reveals TKT as a potential biomarker for medulloblastoma

Sci Rep. 2024 Sep 10;14(1):21053. doi: 10.1038/s41598-024-71738-z.

Authors

Joo Whan Kim^#^{1

2}, Seung Ah Choi^#^{1

2}, Kisoon Dan^#³, Eun Jung Koh^{1

2}, Saehim Ha^{1

2}, Ji Hoon Phi^{1

2

4}, Kyung Hyun Kim^{1

2}, Dohyun Han^{5

6}, Seung-Ki Kim^{7

8

9}

Affiliations

¹ Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.
² Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
³ Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
⁴ Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
⁵ Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea. [email protected].
⁶ Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul, 03082, South Korea. [email protected].
⁷ Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. [email protected].
⁸ Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea. [email protected].
⁹ Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, South Korea. [email protected].

^# Contributed equally.

Abstract

Cerebrospinal fluid (CSF) plays an important role in brain tumors, including medulloblastoma (MBL). Recent advancements in mass spectrometry systems and 'Omics' data analysis methods enable unbiased, high proteome depth research. We conducted proteomic profiling of the total CSF in MBL patients with the purpose of finding a potential diagnostic biomarker for MBL. We quantified 1112 proteins per CSF sample. Feature selection identified four elevated soluble proteins (SPTBN1, HSP90AA1, TKT, and NME1-NME2) in MBL CSF. Validation with ELISA confirmed that TKT was significantly elevated in MBL. Additionally, TKT-positive extracellular vesicles were significantly enriched in MBL CSF and correlated with the burden of leptomeningeal seeding. Our results provide insights into the proteomics data of the total CSF of MBL patients. Furthermore, we identified the significance of TKT within the total CSF and its presence within circulating EVs in the CSF. We suggest that TKT may serve as a biomarker for MBL.

MeSH terms

Adolescent
Biomarkers, Tumor* / cerebrospinal fluid
Cerebellar Neoplasms / cerebrospinal fluid
Child
Child, Preschool
Extracellular Vesicles / metabolism
Female
Humans
Male
Medulloblastoma* / cerebrospinal fluid
Proteome
Proteomics* / methods
Tumor Protein, Translationally-Controlled 1

Substances

Biomarkers, Tumor
Tumor Protein, Translationally-Controlled 1
Proteome

Abstract

MeSH terms

Substances

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