Differential Tissue Metabolic Signatures in IgG4-Related Ophthalmic Disease and Orbital Mucosa-Associated Lymphoid Tissue Lymphoma
| Autor: | Yoshihiko Usui, Kinya Tsubota, Hiroyuki Komatsu, Naoya Nezu, Ryo Wakita, Kazuhiko Umazume, Yasuko Aita, Atsumi Tomita, Masaki Asakage, Masahiro Sugimoto, Hiroshi Goto, Hiroyuki Shimizu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Male Pathology genetic structures Malates Paraproteinemias Adipose tissue Mass Spectrometry 0302 clinical medicine hemic and lymphatic diseases Orbital Diseases MALT lymphoma IgG4-related ophthalmic disease Chromatography High Pressure Liquid Aged 80 and over Principal Component Analysis medicine.diagnostic_test Middle Aged Lymphatic system medicine.anatomical_structure machine learning 030220 oncology & carcinogenesis Metabolome Female Anatomy and Pathology/Oncology Adult medicine.medical_specialty Biology lipids 03 medical and health sciences Metabolomics Biopsy medicine Biomarkers Tumor Humans B cell liquid chromatography-mass spectrometry Aged Retrospective Studies Receiver operating characteristic Lymphoma B-Cell Marginal Zone medicine.disease Lymphoma Glycolates 030104 developmental biology ROC Curve Immunoglobulin G Orbital Neoplasms Spermine |
| Zdroj: | Investigative Ophthalmology & Visual Science |
| ISSN: | 1552-5783 0146-0404 |
| Popis: | Purpose To identify tissue metabolomic profiles in biopsy specimens with IgG4-related ophthalmic disease (IgG4-ROD) and mucosa-associated lymphoid tissue (MALT) lymphoma and investigate their potential implication in the disease pathogenesis and biomarkers. Methods We conducted a comprehensive analysis of the metabolomes and lipidomes of biopsy-proven IgG4-ROD (n = 22) and orbital MALT lymphoma (n = 21) specimens and matched adjacent microscopically normal adipose tissues using liquid chromatography time-of-flight mass spectrometry. The altered metabolomic profiles were visualized by heat map and principal component analysis. Metabolic pathway analysis was performed by Metabo Analyst 4.0 using differentially expressed metabolites. The diagnostic performance of the metabolic markers was evaluated using receiver operating characteristic curves. Machine learning algorithms were implemented by random forest using the R environment. Finally, an independent set of 18 IgG4-ROD and 17 orbital MALT lymphoma specimens were used to validate the identified biomarkers. Results The principal component analysis showed a significant difference of both IgG4-ROD and orbital MALT lymphoma for biopsy specimens and controls. Interestingly, lesions in IgG4-ROD were uniquely enriched in arachidonic metabolism, whereas those in orbital MALT lymphoma were enriched in tricarboxylic acid cycle metabolism. We identified spermine as the best discriminator between IgG4-ROD and orbital MALT lymphoma, and the area under the receiver operating characteristic curve of the spermine to discriminate between the two diseases was 0.89 (95% confidence interval, 0.803-0.984). A random forest model incorporating a panel of five metabolites showed a high area under the receiver operating characteristic curve value of 0.983 (95% confidence interval, 0.981-0.984). The results of validation revealed that four tissue metabolites: N1,N12-diacetylspermine, spermine, malate, and glycolate, had statistically significant differences between IgG4-ROD and orbital MALT lymphoma with receiver operating characteristic values from 0.708 to 0.863. Conclusions These data revealed the characteristic differences in metabolomic profiles between IgG4-ROD and orbital MALT lymphoma, which may be useful for developing new diagnostic biomarkers and elucidating the pathogenic mechanisms of these common orbital lymphoproliferative disorders. |
| Databáze: | OpenAIRE |
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