Lipid Metabolic-Related Signature CYP19A1 is a Potential Biomarker for Prognosis and Immune Cell Infiltration in Gastric Cancer

Abstract

Background: Altered lipid metabolism is associated with gastric cancer (GC) progression. Comprehensive analysis to identify critical lipid metabolic drivers for predicting overall survival (OS) is not fully elucidated in GC. Our study aim to explore a novel lipid metabolism-related prognostic marker for GC. Methods: Transcriptional status and clinical features were obtained from the TCGA-STAD database. The differentially expressed lipid metabolic genes and the risk prognostic model were developed by using bioinformatics and Cox regression analyses. ROC and Kaplan-Meier analysis were established to assess the performance of the risk predictive score model. GSE84437 dataset was used for external validation. Immunochemistry (IHC) was used to examine the expression of CYP19A1 in GC patients. Gene Set Enrichment Analysis (GSEA) was conducted to elucidate the underlying enriched mechanisms. TIMER and CIBERSORT analysis were performed to explore the relationship between CYP19A1 and immune microenvironment. Results: A novel lipid metabolic gene signature (including MTTP, CYP19A1, MYB, SERPINE1), and specifically CYP19A1, might be a promising prognostic factor for GC. Using the validation cohort, ROC curves indicate a good showing of our risk model. Based on the signature yielded a significant difference OS time between the low-and high-risk groups. Cox regression indicates that the signature is an independent prognostic variable. ROC curves present better and reliability predictive accuracy. The IHC data validate that high expression of CYP19A1 was found in GC tissues. GSEA analysis reveals that higher expression of CYP19A1 may significantly up-regulate genes involved in fatty acid metabolism and glycerolipid metabolism. CIBERSORT analysis suggests that CYP19A1 is related to the infiltration of multiple immune cells. Conclusion: CYP19A1 could be an independent prognostic factor and a novel metabolic-targeted treatment strategy for gastric cancer.

Integrated analysis of single-cell and bulk RNA-sequencing reveals a novel signature based on NK cell marker genes to predict prognosis and immunotherapy response in gastric cancer

“…MAGEA11 was previously found to be highly expressed in breast cancer, bladder cancer, and laryngeal squamous cell carcinoma 26 – 28 ; the positive expression of this gene was associated with the progression of malignant tumors, thus leading to poor survival 29 , 30 . CYP19A1 , a member of the cytochrome P450 family, was previously found to be highly expressed in GC and associated with an adverse prognosis; the silencing of its expression could be useful for GC treatment 31 , 32 . A previous study showed that SHOX2 methylation represent a potential biomarker for some cancers 33 – 37 .…”

Progressions of the correlation between lipid metabolism and immune infiltration characteristics in gastric cancer and identification of BCHE as a potential biomarker

“…In prostate cancer, BCHE expression is down-regulated early on and up-regulated in the late stage ( 75 ). Cytochrome P450 family 19 subfamily A member 1 (CYP19A1) can catalyze the conversion of androgen/testosterone to estradiol/estrone, the main enzyme involved in estrogen production ( 76 ). Breast cancer, endometrial cancer, and Alzheimer’s disease are intimately associated with CYP19A1 ( 77 – 79 ).…”

Identification of the Mechanism of Action of the Index Components of Banxia Xiexin Decoction for Gastric Cancer through Network Pharmacology, Bioinformatics, and Molecular Docking Analysis

“…CYP19A1 catalyzes the synthesis of steroids, which are involved in the development of gastric cancer [29]. Based on immunohistochemistry fndings, CYP19A1 has been reported to be upregulated in gastric cancer tissues, and it has been suggested as an independent biomarker for gastric cancer [30]. Phytomedicines that induce downregulated CYP19A1, such as ursolic acid and taxifolin, reduce the malignancy and progression of gastric cancer [31,32].…”