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

Abstract

BackgroundLung 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.MethodsBased 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.ResultsBased 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.ConclusionThe 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.

Characterization and validation of fatty acid metabolism‐related genes predicting prognosis, immune infiltration, and drug sensitivity in endometrial cancer

“…It has been shown that in mice, deletion of the gene encoding HPGDS affects pancreatic cancer development. 47 Our study is consistent with existing studies that modulation of ACOXL, EPHX2, and HPGDS has a more pronounced effect on the developmental process of endometrial cancer, and its mechanism of action needs to be further explored.…”

Tumour specimen cold ischemia time impacts molecular cancer drug target discovery

“…These pathways reveal a coping mechanism involving decrease in expression of proteins that are either not survival-critical under metabolic stress induced by ischemia (such as proteins involved in drug metabolism like UGT2B17 or UGT1A8) or those that are energy intensive for the cell (ribosome biogenesis). Ischemia very interestingly appears to slowly breach through this coping mechanism by causing a decrease in tumour survival-critical proteins such as NUDT1, ELOVL, HPGDS or DZIP3 [8, 9, 10, 11].…”

Screening of Lipid Metabolism-Related Genes as Diagnostic Indicators in Chronic Obstructive Pulmonary Disease

“…The hematopoietic prostaglandin D synthase ( HPGDS ) is a σ-like glutathione transferase that participates in the arachidonic acid metabolic pathway and catalyzes the production of prostaglandin D2, which is an important mediator of inflammation and malignant tumor growth. According to Shao et al 34 mutations of HPGDS promote lung cancer cell migration by upregulating the expression of ACSL1 and ACC, important enzymes involved in lipid metabolism. In type 2 diabetic mice, HPGDS was significantly downregulated in wounds, and its deficiency delayed normal wound healing.…”