Metabolomic Profiling Reveals That 5-Hydroxylysine and 1-Methylnicotinamide Are Metabolic Indicators of Keloid Severity

Background: Keloid is a skin fibroproliferative disease with unknown pathogenesis. Metabolomics provides a new perspective for revealing biomarkers related to metabolites and their metabolic mechanisms.Method: Metabolomics and transcriptomics were used for data analysis. Quality control of the data...

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Main Authors: Mengjie Shan, Hao Liu, Yan Hao, Kexin Song, Tian Meng, Cheng Feng, Youbin Wang, Yongsheng Huang
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-02-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2021.804248/full
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author Mengjie Shan
Mengjie Shan
Hao Liu
Hao Liu
Yan Hao
Yan Hao
Kexin Song
Tian Meng
Cheng Feng
Youbin Wang
Yongsheng Huang
author_facet Mengjie Shan
Mengjie Shan
Hao Liu
Hao Liu
Yan Hao
Yan Hao
Kexin Song
Tian Meng
Cheng Feng
Youbin Wang
Yongsheng Huang
author_sort Mengjie Shan
collection DOAJ
description Background: Keloid is a skin fibroproliferative disease with unknown pathogenesis. Metabolomics provides a new perspective for revealing biomarkers related to metabolites and their metabolic mechanisms.Method: Metabolomics and transcriptomics were used for data analysis. Quality control of the data was performed to standardize the data. Principal component analysis (PCA), PLS-DA, OPLS-DA, univariate analysis, CIBERSORT, neural network model, and machine learning correlation analysis were used to calculate differential metabolites. The molecular mechanisms of characteristic metabolites and differentially expressed genes were identified through enrichment analysis and topological analysis.Result: Compared with normal tissue, lipids have a tendency to decrease in keloids, while peptides have a tendency to increase in keloids. Significantly different metabolites between the two groups were identified by random forest analysis, including 1-methylnicotinamide, 4-hydroxyproline, 5-hydroxylysine, and l-prolinamide. The metabolic pathways which play important roles in the pathogenesis of keloids included arachidonic acid metabolism and d-arginine and d-ornithine metabolism. Metabolomic profiling reveals that 5-hydroxylysine and 1-methylnicotinamide are metabolic indicators of keloid severity. The high-risk early warning index for 5-hydroxylysine is 4 × 108-6.3×108 (p = 0.0008), and the high-risk predictive index for 1-methylnicotinamide is 0.95 × 107-1.6×107 (p = 0.0022).Conclusion: This study was the first to reveal the metabolome profile and transcriptome of keloids. Differential metabolites and metabolic pathways were calculated by machine learning. Metabolomic profiling reveals that 5-hydroxylysine and 1-methylnicotinamide may be metabolic indicators of keloid severity.
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spelling doaj.art-3333db41d2ca4ea583a2fd59d7b30edd2022-12-21T23:44:21ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-02-011210.3389/fgene.2021.804248804248Metabolomic Profiling Reveals That 5-Hydroxylysine and 1-Methylnicotinamide Are Metabolic Indicators of Keloid SeverityMengjie Shan0Mengjie Shan1Hao Liu2Hao Liu3Yan Hao4Yan Hao5Kexin Song6Tian Meng7Cheng Feng8Youbin Wang9Yongsheng Huang10Department of Plastic Surgery, Peking Union Medical College Hospital, Beijing, ChinaGraduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Plastic Surgery, Peking Union Medical College Hospital, Beijing, ChinaGraduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Plastic Surgery, Peking Union Medical College Hospital, Beijing, ChinaGraduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Plastic Surgery, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Plastic Surgery, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Plastic Surgery, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Plastic Surgery, Peking Union Medical College Hospital, Beijing, ChinaGraduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaBackground: Keloid is a skin fibroproliferative disease with unknown pathogenesis. Metabolomics provides a new perspective for revealing biomarkers related to metabolites and their metabolic mechanisms.Method: Metabolomics and transcriptomics were used for data analysis. Quality control of the data was performed to standardize the data. Principal component analysis (PCA), PLS-DA, OPLS-DA, univariate analysis, CIBERSORT, neural network model, and machine learning correlation analysis were used to calculate differential metabolites. The molecular mechanisms of characteristic metabolites and differentially expressed genes were identified through enrichment analysis and topological analysis.Result: Compared with normal tissue, lipids have a tendency to decrease in keloids, while peptides have a tendency to increase in keloids. Significantly different metabolites between the two groups were identified by random forest analysis, including 1-methylnicotinamide, 4-hydroxyproline, 5-hydroxylysine, and l-prolinamide. The metabolic pathways which play important roles in the pathogenesis of keloids included arachidonic acid metabolism and d-arginine and d-ornithine metabolism. Metabolomic profiling reveals that 5-hydroxylysine and 1-methylnicotinamide are metabolic indicators of keloid severity. The high-risk early warning index for 5-hydroxylysine is 4 × 108-6.3×108 (p = 0.0008), and the high-risk predictive index for 1-methylnicotinamide is 0.95 × 107-1.6×107 (p = 0.0022).Conclusion: This study was the first to reveal the metabolome profile and transcriptome of keloids. Differential metabolites and metabolic pathways were calculated by machine learning. Metabolomic profiling reveals that 5-hydroxylysine and 1-methylnicotinamide may be metabolic indicators of keloid severity.https://www.frontiersin.org/articles/10.3389/fgene.2021.804248/fullkeloidmetabolomicrandom forestPLS-DAmachine learningneural network model
spellingShingle Mengjie Shan
Mengjie Shan
Hao Liu
Hao Liu
Yan Hao
Yan Hao
Kexin Song
Tian Meng
Cheng Feng
Youbin Wang
Yongsheng Huang
Metabolomic Profiling Reveals That 5-Hydroxylysine and 1-Methylnicotinamide Are Metabolic Indicators of Keloid Severity
Frontiers in Genetics
keloid
metabolomic
random forest
PLS-DA
machine learning
neural network model
title Metabolomic Profiling Reveals That 5-Hydroxylysine and 1-Methylnicotinamide Are Metabolic Indicators of Keloid Severity
title_full Metabolomic Profiling Reveals That 5-Hydroxylysine and 1-Methylnicotinamide Are Metabolic Indicators of Keloid Severity
title_fullStr Metabolomic Profiling Reveals That 5-Hydroxylysine and 1-Methylnicotinamide Are Metabolic Indicators of Keloid Severity
title_full_unstemmed Metabolomic Profiling Reveals That 5-Hydroxylysine and 1-Methylnicotinamide Are Metabolic Indicators of Keloid Severity
title_short Metabolomic Profiling Reveals That 5-Hydroxylysine and 1-Methylnicotinamide Are Metabolic Indicators of Keloid Severity
title_sort metabolomic profiling reveals that 5 hydroxylysine and 1 methylnicotinamide are metabolic indicators of keloid severity
topic keloid
metabolomic
random forest
PLS-DA
machine learning
neural network model
url https://www.frontiersin.org/articles/10.3389/fgene.2021.804248/full
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