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Plasma lipids signify the progression of precancerous gastric lesions to gastric cancer: a prospective targeted lipidomics study
Rationale: Gastric cancer (GC) is preceded by a stepwise progression of precancerous gastric lesions. Distinguishing individuals with precancerous gastric lesions that have progression potential to GC is an important need. Perturbated lipid metabolism, particularly the dysregulation of de novo lipog...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254242/ https://www.ncbi.nlm.nih.gov/pubmed/35832080 http://dx.doi.org/10.7150/thno.74770 |
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author | Liu, Zong-Chao Wu, Wen-Hui Huang, Sha Li, Zhong-Wu Li, Xue Shui, Guang-Hou Lam, Sin Man Li, Bo-Wen Li, Zhe-Xuan Zhang, Yang Zhou, Tong You, Wei-Cheng Pan, Kai-Feng Li, Wen-Qing |
author_facet | Liu, Zong-Chao Wu, Wen-Hui Huang, Sha Li, Zhong-Wu Li, Xue Shui, Guang-Hou Lam, Sin Man Li, Bo-Wen Li, Zhe-Xuan Zhang, Yang Zhou, Tong You, Wei-Cheng Pan, Kai-Feng Li, Wen-Qing |
author_sort | Liu, Zong-Chao |
collection | PubMed |
description | Rationale: Gastric cancer (GC) is preceded by a stepwise progression of precancerous gastric lesions. Distinguishing individuals with precancerous gastric lesions that have progression potential to GC is an important need. Perturbated lipid metabolism, particularly the dysregulation of de novo lipogenesis, is involved in gastric carcinogenesis. We conducted the first prospective lipidomics study exploring lipidomic signatures for the risk of gastric lesion progression and early GC. Methods: Our two-stage study of targeted lipidomics enrolled 400 subjects from the National Upper Gastrointestinal Cancer Early Detection Program in China, including 200 subjects of GC and different gastric lesions in the discovery and validation stages. Of validation stage, 152 cases with gastric lesions were prospectively followed for the progression of gastric lesions for a median follow-up of 580 days (interquartile range 390-806 days). We examined the lipidomic signatures associated with the risk of advanced gastric lesions and their progression to GC. Our published tissue proteomic data were referred to further investigate highlighted lipids with their biologically related protein expression in gastric mucosa. Results: We identified 11 plasma lipids significantly inversely associated with the risk of gastric lesion progression and GC occurrence. These lipids were integrated as latent profiles to identify 5 clusters of lipid expression that had distinct risk of gastric lesion progression. The latent profiles significantly improved the ability to predict the progression potential of gastric lesions (AUC: 0.82 vs 0.68, Delong's P = 4.6×10(-4)) and risk of early GC (AUC: 0.81 vs 0.55, P = 6.3×10(-5)). Significant associations were found between highlighted lipids, their biologically correlated proteins and the risk of GC, supporting the role of the pathways involving monocarboxylic acid metabolism and lipid transport and catabolic process in GC. Conclusions: Our study revealed the lipidomic signatures associated with the risk of gastric lesion progression and GC occurrence, exhibiting translational implications for GC prevention. |
format | Online Article Text |
id | pubmed-9254242 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-92542422022-07-12 Plasma lipids signify the progression of precancerous gastric lesions to gastric cancer: a prospective targeted lipidomics study Liu, Zong-Chao Wu, Wen-Hui Huang, Sha Li, Zhong-Wu Li, Xue Shui, Guang-Hou Lam, Sin Man Li, Bo-Wen Li, Zhe-Xuan Zhang, Yang Zhou, Tong You, Wei-Cheng Pan, Kai-Feng Li, Wen-Qing Theranostics Research Paper Rationale: Gastric cancer (GC) is preceded by a stepwise progression of precancerous gastric lesions. Distinguishing individuals with precancerous gastric lesions that have progression potential to GC is an important need. Perturbated lipid metabolism, particularly the dysregulation of de novo lipogenesis, is involved in gastric carcinogenesis. We conducted the first prospective lipidomics study exploring lipidomic signatures for the risk of gastric lesion progression and early GC. Methods: Our two-stage study of targeted lipidomics enrolled 400 subjects from the National Upper Gastrointestinal Cancer Early Detection Program in China, including 200 subjects of GC and different gastric lesions in the discovery and validation stages. Of validation stage, 152 cases with gastric lesions were prospectively followed for the progression of gastric lesions for a median follow-up of 580 days (interquartile range 390-806 days). We examined the lipidomic signatures associated with the risk of advanced gastric lesions and their progression to GC. Our published tissue proteomic data were referred to further investigate highlighted lipids with their biologically related protein expression in gastric mucosa. Results: We identified 11 plasma lipids significantly inversely associated with the risk of gastric lesion progression and GC occurrence. These lipids were integrated as latent profiles to identify 5 clusters of lipid expression that had distinct risk of gastric lesion progression. The latent profiles significantly improved the ability to predict the progression potential of gastric lesions (AUC: 0.82 vs 0.68, Delong's P = 4.6×10(-4)) and risk of early GC (AUC: 0.81 vs 0.55, P = 6.3×10(-5)). Significant associations were found between highlighted lipids, their biologically correlated proteins and the risk of GC, supporting the role of the pathways involving monocarboxylic acid metabolism and lipid transport and catabolic process in GC. Conclusions: Our study revealed the lipidomic signatures associated with the risk of gastric lesion progression and GC occurrence, exhibiting translational implications for GC prevention. Ivyspring International Publisher 2022-06-06 /pmc/articles/PMC9254242/ /pubmed/35832080 http://dx.doi.org/10.7150/thno.74770 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Liu, Zong-Chao Wu, Wen-Hui Huang, Sha Li, Zhong-Wu Li, Xue Shui, Guang-Hou Lam, Sin Man Li, Bo-Wen Li, Zhe-Xuan Zhang, Yang Zhou, Tong You, Wei-Cheng Pan, Kai-Feng Li, Wen-Qing Plasma lipids signify the progression of precancerous gastric lesions to gastric cancer: a prospective targeted lipidomics study |
title | Plasma lipids signify the progression of precancerous gastric lesions to gastric cancer: a prospective targeted lipidomics study |
title_full | Plasma lipids signify the progression of precancerous gastric lesions to gastric cancer: a prospective targeted lipidomics study |
title_fullStr | Plasma lipids signify the progression of precancerous gastric lesions to gastric cancer: a prospective targeted lipidomics study |
title_full_unstemmed | Plasma lipids signify the progression of precancerous gastric lesions to gastric cancer: a prospective targeted lipidomics study |
title_short | Plasma lipids signify the progression of precancerous gastric lesions to gastric cancer: a prospective targeted lipidomics study |
title_sort | plasma lipids signify the progression of precancerous gastric lesions to gastric cancer: a prospective targeted lipidomics study |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254242/ https://www.ncbi.nlm.nih.gov/pubmed/35832080 http://dx.doi.org/10.7150/thno.74770 |
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