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基于谷氨酰胺代谢相关基因的卵巢癌不同亚型鉴定及预后模型构建

Identification of different subtypes of ovarian cancer and construction of prognostic models based on glutamine-metabolism associated genes.

作者信息

Yaqing Xie, Yang Gao, Linlin Yang, Youqing Ruan, Henghui Yang, Ping Yang, Hongying Yang, Shaojia Wang

机构信息

Department of Gynecology, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, Kunming 650118, China.

出版信息

Heliyon. 2024 Mar 11;10(6):e27358. doi: 10.1016/j.heliyon.2024.e27358. eCollection 2024 Mar 30.

Abstract

Ovarian cancer (OC) is common malignant tumor of female reproductive system. Glutamine metabolism-related genes (GMRGs) play a key role in ovarian cancer. Here, available database-- The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases were applied in our research. OC samples from TCGA were divided into different clusters based on Cox analysis, which filtering GMRGs with survival information. Then, differentially expressed genes (DEGs) between these clusters were intersected with DEGs between normal ovary samples and OC samples, and GMRGs in order to obtain GMRGs-related DEGs. Next, a risk model of OC was constructed and enrichment analysis of risk model was performed based on hallmark gene set. Besides, the immune cells ratio in OC samples were detected via Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT). Finally, we explored a series of potential biomarkers of OC. In this research, 9 GMRGs-related DEGs were obtained. GMRGs-related DEGs were enriched to canonical Wnt signaling pathway.NKD2, C2orf88, and KLHDC8A, which were significantly associated with prognosis, were retained for risk model construction. Based on the risk model, 18 hallmark pathways with significant difference were enriched. Fifteen types of immune cells (such as iDC, NK CD56dim cells, and neutrophils) enjoying significant difference between these 2 risk groups (high risk group low risk group) were detected, which indicates possible disparate TME in different metabolic subtypes of ovarian cancer.

摘要

卵巢癌(OC)是女性生殖系统常见的恶性肿瘤。谷氨酰胺代谢相关基因(GMRGs)在卵巢癌中起关键作用。在此,我们的研究应用了可用数据库——癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)和基因表达综合数据库(GEO)。基于Cox分析将来自TCGA的OC样本分为不同簇,筛选出具有生存信息的GMRGs。然后,将这些簇之间的差异表达基因(DEGs)与正常卵巢样本和OC样本之间的DEGs以及GMRGs进行交集分析,以获得GMRGs相关的DEGs。接下来,构建OC风险模型,并基于标志性基因集对风险模型进行富集分析。此外,通过基于RNA转录本相对子集估计的细胞类型鉴定(CIBERSORT)检测OC样本中的免疫细胞比例。最后,我们探索了一系列OC潜在生物标志物。本研究中,获得了9个GMRGs相关的DEGs。GMRGs相关的DEGs富集到经典Wnt信号通路。与预后显著相关的NKD2、C2orf​​88和KLHDC8A被保留用于构建风险模型。基于该风险模型,富集了18条具有显著差异的标志性通路。检测到这两个风险组(高风险组和低风险组)之间15种免疫细胞(如未成熟树突状细胞、自然杀伤CD56dim细胞和中性粒细胞)存在显著差异,这表明卵巢癌不同代谢亚型的肿瘤微环境可能不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a927/10950510/1973b2744736/gr1.jpg

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