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分析和实验验证脂肪酸代谢相关基因前列环素合酶(PTGIS)在子宫内膜癌中的作用。

Analysis and experimental validation of fatty acid metabolism-related genes prostacyclin synthase (PTGIS) in endometrial cancer.

机构信息

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110000, Liaoning, People’s Republic of China.

出版信息

Aging (Albany NY). 2023 Oct 4;15(19):10322-10346. doi: 10.18632/aging.205080.

Abstract

The deregulation of fatty acid metabolism plays a pivotal role in cancer. Our objective is to construct a prognostic model for patients with endometrial carcinoma (EC) based on genes related to fatty acid metabolism-related genes (FAMGs). RNA sequencing and clinical data for EC were obtained from The Cancer Genome Atlas (TCGA). Lasso-Penalized Cox regression was employed to derive the risk formula for the model, the score = e. Gene set enrichment analysis (GSEA) was utilized to examine the enrichment of KEGG and GO pathways within this model. Correlation analysis of immune function was conducted using Single-sample GSEA (ssGSEA). The "ESTIMATE" package in R was utilized to evaluate the tumor microenvironment. The support vector machine recursive feature elimination (SVM-RFE) and randomforest maps were employed to identify key genes. The effects of PTGIS on the malignant biological behavior of EC were assessed through CCK-8 assay, transwell invasion assay, cell cycle analysis, apoptosis assay, and tumor xenografts in nude mice. A novel prognostic signature comprising 10 FAMGs (INMT, ACACB, ACOT4, ACOXL, CYP4F3, FAAH, GPX1, HPGDS, PON3, PTGIS) was developed. This risk score serves as an independent prognostic marker validated for EC. According to ssGSEA analysis, the low- and high-risk groups exhibited distinct immune enrichments. The key gene PTGIS was screened by SVM-RFE and randomforest method. Furthermore, we validated the expression of PTGIS through qRT-PCR. and experiments also confirmed the effect of PTGIS on the malignant biological behavior of EC.

摘要

脂肪酸代谢失调在癌症中起着关键作用。我们的目的是基于与脂肪酸代谢相关基因(FAMGs)构建子宫内膜癌(EC)患者的预后模型。从癌症基因组图谱(TCGA)获得了 EC 的 RNA 测序和临床数据。Lasso-Penalized Cox 回归用于推导模型的风险公式,得分=e。使用基因集富集分析(GSEA)检查该模型中 KEGG 和 GO 途径的富集情况。使用单样本 GSEA(ssGSEA)进行免疫功能的相关性分析。使用 R 中的“ESTIMATE”包评估肿瘤微环境。支持向量机递归特征消除(SVM-RFE)和随机森林图谱用于识别关键基因。通过 CCK-8 测定、Transwell 侵袭测定、细胞周期分析、凋亡测定和裸鼠肿瘤异种移植评估 PTGIS 对 EC 恶性生物学行为的影响。开发了一个包含 10 个 FAMGs(INMT、ACACB、ACOT4、ACOXL、CYP4F3、FAAH、GPX1、HPGDS、PON3、PTGIS)的新的预后特征。该风险评分可作为 EC 的独立预后标志物进行验证。根据 ssGSEA 分析,低风险组和高风险组表现出不同的免疫富集。通过 SVM-RFE 和随机森林方法筛选关键基因 PTGIS。此外,我们通过 qRT-PCR 验证了 PTGIS 的表达。和实验还证实了 PTGIS 对 EC 恶性生物学行为的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8793/10599728/b664de58355b/aging-15-205080-g001.jpg

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