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

Joo Whan Kim ^1,2, Seung Ah Choi ^1,2, Kisoon Dan ³

¹Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.
²Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
³Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
⁴Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
⁵Proteomics Core Facility, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea. hdh03@snu.ac.kr.
⁶Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul, 03082, South Korea. hdh03@snu.ac.kr.
⁷Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. nsthomas@snu.ac.kr.
⁸Department of Neurosurgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea. nsthomas@snu.ac.kr.
⁹Neuroscience Research Institute, Seoul National University College of Medicine, Seoul, South Korea. nsthomas@snu.ac.kr.

⁰Division of Pediatric Neurosurgery, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.

Scientific Reports +

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September 9, 2024

View abstract on PubMed

Summary

Researchers identified Tissue-tensioning kinase (TKT) as a potential biomarker for medulloblastoma (MBL). TKT was elevated in cerebrospinal fluid (CSF) and extracellular vesicles of MBL patients, suggesting its diagnostic utility.

Area Of Science

Neuro-oncology
Proteomics
Biomarker Discovery

Background

Cerebrospinal fluid (CSF) is crucial in understanding brain tumors like medulloblastoma (MBL).
Advanced mass spectrometry and 'Omics' enable deep proteomic analysis of CSF.
Identifying reliable biomarkers for MBL is essential for early diagnosis and treatment.

Purpose Of The Study

To perform proteomic profiling of CSF in medulloblastoma patients.
To identify potential diagnostic protein biomarkers for MBL.
To investigate the role of identified proteins in MBL pathogenesis and spread.

Main Methods

Proteomic profiling of total CSF from MBL patients and controls using mass spectrometry.
Quantification of over 1100 proteins per sample.
Validation of candidate biomarkers using Enzyme-Linked Immunosorbent Assay (ELISA) and analysis of extracellular vesicles (EVs).

Main Results

Quantified 1112 proteins in CSF samples.
Identified four significantly elevated soluble proteins in MBL CSF: SPTBN1, HSP90AA1, TKT, and NME1-NME2.
Validated TKT as significantly elevated in MBL CSF via ELISA.
Found TKT-positive EVs enriched in MBL CSF, correlating with leptomeningeal seeding.

Conclusions

Proteomic analysis of CSF provides valuable insights into medulloblastoma.
Tissue-tensioning kinase (TKT) is significantly elevated in MBL CSF and within circulating EVs.
TKT shows promise as a potential diagnostic biomarker for medulloblastoma.