Identification of Metabolomic Markers in Frozen or Formalin-Fixed and Paraffin-Embedded Samples of Diffuse Glioma from Adults
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Metabolomic Markers of the Gliomagenesis Pathway: IDH-Mutant versus IDH-Wild-Type Tumors
2.2. Metabolomic Markers of Grade: Grade 4 versus Lower Grades
2.3. A First Analysis Included Both IDH-Mutant and IDH-Wild-Type Tumors
2.4. In an Additional Step, IDH-Mutant and IDH-Wild-Type Astrocytomas Were Separately Analyzed
2.4.1. Concerning IDH-Mutant Astrocytomas
2.4.2. Concerning IDH-Wild-Type Astrocytomas
3. Discussion
- We filtered the initial raw data, removing peaks of lower intensities. This step aims to denoise the data but could also discard metabolites of interest with low concentrations.
- We used a constrained statistical method, the LASSO penalized logistic regression, which is robust to correlated features and to overfitting.
- We systematically verified the identification of the selected ions by comparing the obtained mass/charge ratios with mass spectrometry databases and by comparing the corresponding MS/MS spectrums to spectrum databases.
- We verified the results obtained using the frozen sample cohort using the FFPE sample cohort, which we used as a validation dataset.
4. Materials and Methods
4.1. Sample Collection
4.2. Sample Preparation
4.3. LC-MS/MS Analysis
4.4. Metabolomic Profiling
4.5. Statistical Analyses
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Histological Subtypes | IDH Status | WHO 2021 Grade | WHO 2007 Grade | Frozen Samples n = 87 (%) | FFPE Samples n = 126 (%) |
---|---|---|---|---|---|
Oligodendroglioma | Mutant | 2 | II | 7 (8.0%) | 15 (11.9%) |
Astrocytoma | Mutant | 2 | II | 19 (21.8%) | 29 (23.0%) |
Astrocytoma | Mutant | 3 | III | 10 (11.5%) | 15 (11.9%) |
Astrocytoma | Mutant | 4 | IV | 12 (13.8%) | 16 (12.7%) |
Astrocytoma * | Wild type | 4 | II | 9 (10.3%) | 15 (11.9%) |
Astrocytoma * | Wild type | 4 | III | 12 (13.8%) | 20 (15.9%) |
Glioblastoma | Wild type | 4 | IV | 18 (20.7%) | 16 (12.7%) |
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Chardin, D.; Jing, L.; Chazal-Ngo-Mai, M.; Guigonis, J.-M.; Rigau, V.; Goze, C.; Duffau, H.; Virolle, T.; Pourcher, T.; Burel-Vandenbos, F. Identification of Metabolomic Markers in Frozen or Formalin-Fixed and Paraffin-Embedded Samples of Diffuse Glioma from Adults. Int. J. Mol. Sci. 2023, 24, 16697. https://doi.org/10.3390/ijms242316697
Chardin D, Jing L, Chazal-Ngo-Mai M, Guigonis J-M, Rigau V, Goze C, Duffau H, Virolle T, Pourcher T, Burel-Vandenbos F. Identification of Metabolomic Markers in Frozen or Formalin-Fixed and Paraffin-Embedded Samples of Diffuse Glioma from Adults. International Journal of Molecular Sciences. 2023; 24(23):16697. https://doi.org/10.3390/ijms242316697
Chicago/Turabian StyleChardin, David, Lun Jing, Mélanie Chazal-Ngo-Mai, Jean-Marie Guigonis, Valérie Rigau, Catherine Goze, Hugues Duffau, Thierry Virolle, Thierry Pourcher, and Fanny Burel-Vandenbos. 2023. "Identification of Metabolomic Markers in Frozen or Formalin-Fixed and Paraffin-Embedded Samples of Diffuse Glioma from Adults" International Journal of Molecular Sciences 24, no. 23: 16697. https://doi.org/10.3390/ijms242316697