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HPGDS is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common respiratory globallywith a poor prognosis. Lipid metabolism is extremely important for the occurrence and development of cancer. However, the role of genes involved in lipid metabolism in LUAD development is unclear. We aimed to identify the...

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Autores principales: Shao, Fengling, Mao, Huajie, Luo, Tengling, Li, Qijun, Xu, Lei, Xie, Yajun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618883/
https://www.ncbi.nlm.nih.gov/pubmed/36324576
http://dx.doi.org/10.3389/fonc.2022.894485
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author Shao, Fengling
Mao, Huajie
Luo, Tengling
Li, Qijun
Xu, Lei
Xie, Yajun
author_facet Shao, Fengling
Mao, Huajie
Luo, Tengling
Li, Qijun
Xu, Lei
Xie, Yajun
author_sort Shao, Fengling
collection PubMed
description BACKGROUND: Lung adenocarcinoma (LUAD) is the most common respiratory globallywith a poor prognosis. Lipid metabolism is extremely important for the occurrence and development of cancer. However, the role of genes involved in lipid metabolism in LUAD development is unclear. We aimed to identify the abnormal lipid metabolism pathway of LUAD, construct a novel prognostic model of LUAD, and discover novel biomarkers involved in lipid metabolism in LUAD. METHODS: Based on differentially expressed genes involved in lipid metabolism in LUAD samples from The Cancer Genome Atlas (TCGA), abnormal lipid metabolism pathways in LUAD were analyzed. The lasso penalized regression analysis was performed on the TCGA cohort (training set) to construct a risk score formula. The predictive ability of the risk score was validated in the Gene Expression Omnibus (GEO) dataset (validation set) using Kaplan-Meier analysis and ROC curves. Finally, based on CRISPR gene editing technology, hematopoietic prostaglandin D synthase (HPGDS) was knocked out in A549 cell lines, the changes in lipid metabolism-related markers were detected by western blotting, and the changes in cell migration were detected by transwell assay. RESULTS: Based on the differential genes between lung cancer tissue and normal tissue, we found that the arachidonic acid metabolism pathway is an abnormal lipid metabolism pathway in both lung adenocarcinoma and lung squamous cell carcinoma. Based on the sample information of TCGA and abnormally expressed lipid metabolism-related genes, a 9-gene prognostic risk score was successfully constructed and validated in the GEO dataset. Finally, we found that knockdown of HPGDS in A549 cell lines promoted lipid synthesis and is more invasive than in control cells. Rescue assays showed that ACSL1 knockdown reversed the pro-migration effects of HPGDS knockdown. The knockdown of HPGDS promoted migration response by upregulating the expression of the lipid metabolism key enzymes ACSL1 and ACC. CONCLUSION: The genes involved in lipid metabolism are associated with the occurrence and development of LUAD. HPGDS can be a therapeutic target of a potential lipid metabolism pathway in LUAD, and the therapeutic target of lipid metabolism genes in LUAD should be studied further.
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spelling pubmed-96188832022-11-01 HPGDS is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma Shao, Fengling Mao, Huajie Luo, Tengling Li, Qijun Xu, Lei Xie, Yajun Front Oncol Oncology BACKGROUND: Lung adenocarcinoma (LUAD) is the most common respiratory globallywith a poor prognosis. Lipid metabolism is extremely important for the occurrence and development of cancer. However, the role of genes involved in lipid metabolism in LUAD development is unclear. We aimed to identify the abnormal lipid metabolism pathway of LUAD, construct a novel prognostic model of LUAD, and discover novel biomarkers involved in lipid metabolism in LUAD. METHODS: Based on differentially expressed genes involved in lipid metabolism in LUAD samples from The Cancer Genome Atlas (TCGA), abnormal lipid metabolism pathways in LUAD were analyzed. The lasso penalized regression analysis was performed on the TCGA cohort (training set) to construct a risk score formula. The predictive ability of the risk score was validated in the Gene Expression Omnibus (GEO) dataset (validation set) using Kaplan-Meier analysis and ROC curves. Finally, based on CRISPR gene editing technology, hematopoietic prostaglandin D synthase (HPGDS) was knocked out in A549 cell lines, the changes in lipid metabolism-related markers were detected by western blotting, and the changes in cell migration were detected by transwell assay. RESULTS: Based on the differential genes between lung cancer tissue and normal tissue, we found that the arachidonic acid metabolism pathway is an abnormal lipid metabolism pathway in both lung adenocarcinoma and lung squamous cell carcinoma. Based on the sample information of TCGA and abnormally expressed lipid metabolism-related genes, a 9-gene prognostic risk score was successfully constructed and validated in the GEO dataset. Finally, we found that knockdown of HPGDS in A549 cell lines promoted lipid synthesis and is more invasive than in control cells. Rescue assays showed that ACSL1 knockdown reversed the pro-migration effects of HPGDS knockdown. The knockdown of HPGDS promoted migration response by upregulating the expression of the lipid metabolism key enzymes ACSL1 and ACC. CONCLUSION: The genes involved in lipid metabolism are associated with the occurrence and development of LUAD. HPGDS can be a therapeutic target of a potential lipid metabolism pathway in LUAD, and the therapeutic target of lipid metabolism genes in LUAD should be studied further. Frontiers Media S.A. 2022-10-17 /pmc/articles/PMC9618883/ /pubmed/36324576 http://dx.doi.org/10.3389/fonc.2022.894485 Text en Copyright © 2022 Shao, Mao, Luo, Li, Xu and Xie https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Shao, Fengling
Mao, Huajie
Luo, Tengling
Li, Qijun
Xu, Lei
Xie, Yajun
HPGDS is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma
title HPGDS is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma
title_full HPGDS is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma
title_fullStr HPGDS is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma
title_full_unstemmed HPGDS is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma
title_short HPGDS is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma
title_sort hpgds is a novel prognostic marker associated with lipid metabolism and aggressiveness in lung adenocarcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618883/
https://www.ncbi.nlm.nih.gov/pubmed/36324576
http://dx.doi.org/10.3389/fonc.2022.894485
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