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脂质滴代谢模式的特征鉴定了胃癌的预后和肿瘤微环境浸润。

Characterization of lipid droplet metabolism patterns identified prognosis and tumor microenvironment infiltration in gastric cancer.

作者信息

Liu Mengxiao, Fang Xidong, Wang Haoying, Ji Rui, Guo Qinghong, Chen Zhaofeng, Ren Qian, Wang Yuping, Zhou Yongning

机构信息

The First Clinical Medical College, Lanzhou University, Lanzhou, China.

Department of Gastroenterology, the First Hospital of Lanzhou University, Lanzhou, China.

出版信息

Front Oncol. 2023 Jan 11;12:1038932. doi: 10.3389/fonc.2022.1038932. eCollection 2022.

Abstract

BACKGROUND

Gastric cancer is one of the common malignant tumors of the digestive system worldwide, posing a serious threat to human health. A growing number of studies have demonstrated the important role that lipid droplets play in promoting cancer progression. However, few studies have systematically evaluated the role of lipid droplet metabolism-related genes (LDMRGs) in patients with gastric cancer.

METHODS

We identified two distinct molecular subtypes in the TCGA-STAD cohort based on LDMRGs expression. We then constructed risk prediction scoring models in the TCGA-STAD cohort by lasso regression analysis and validated the model with the GSE15459 and GSE66229 cohorts. Moreover, we constructed a nomogram prediction model by cox regression analysis and evaluated the predictive efficacy of the model by various methods in STAD. Finally, we identified the key gene in LDMRGs, ABCA1, and performed a systematic multi-omics analysis in gastric cancer.

RESULTS

Two molecular subtypes were identified based on LDMRGs expression with different survival prognosis and immune infiltration levels. lasso regression models were effective in predicting overall survival (OS) of gastric cancer patients at 1, 3 and 5 years and were validated in the GEO database with consistent results. The nomogram prediction model incorporated additional clinical factors and prognostic molecules to improve the prognostic predictive value of the current TNM staging system. ABCA1 was identified as a key gene in LDMRGs and multi-omics analysis showed a strong correlation between ABCA1 and the prognosis and immune status of patients with gastric cancer.

CONCLUSION

This study reveals the characteristics and possible underlying mechanisms of LDMRGs in gastric cancer, contributing to the identification of new prognostic biomarkers and providing a basis for future research.

摘要

背景

胃癌是全球消化系统常见的恶性肿瘤之一,对人类健康构成严重威胁。越来越多的研究表明脂滴在促进癌症进展中发挥着重要作用。然而,很少有研究系统地评估脂滴代谢相关基因(LDMRGs)在胃癌患者中的作用。

方法

我们基于LDMRGs表达在TCGA-STAD队列中鉴定出两种不同的分子亚型。然后,我们通过套索回归分析在TCGA-STAD队列中构建风险预测评分模型,并用GSE15459和GSE66229队列验证该模型。此外,我们通过cox回归分析构建列线图预测模型,并在STAD中用多种方法评估该模型的预测效能。最后,我们鉴定出LDMRGs中的关键基因ABCA1,并在胃癌中进行了系统的多组学分析。

结果

基于LDMRGs表达鉴定出两种分子亚型,其具有不同的生存预后和免疫浸润水平。套索回归模型能有效预测胃癌患者1年、3年和5年的总生存期(OS),并在GEO数据库中得到验证,结果一致。列线图预测模型纳入了额外的临床因素和预后分子,以提高当前TNM分期系统的预后预测价值。ABCA1被鉴定为LDMRGs中的关键基因,多组学分析显示ABCA1与胃癌患者的预后和免疫状态密切相关。

结论

本研究揭示了LDMRGs在胃癌中的特征及潜在机制,有助于识别新的预后生物标志物,并为未来研究提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d646/9875057/1c0044f601e6/fonc-12-1038932-g001.jpg

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