肺腺癌中脂质代谢的异质性及其与临床和免疫的相关性。

Heterogeneity of Lipid Metabolism and its Clinical and Immune Correlation in Lung Adenocarcinoma.

机构信息

Department of Thoracic Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100000, China.

出版信息

Curr Med Chem. 2024 Feb 6;31(12):1561-1577. doi: 10.2174/0929867331666230818144416.

DOI:10.2174/0929867331666230818144416

PMID:37594166

Abstract

INTRODUCTION

The role of lipid metabolism in lung adenocarcinoma (LUAD) is not completely researched. Lipid metabolism reprogramming is a characteristic of malignancies and contributes to carcinogenesis and progression. The transcriptome and scRNA- seq data and clinical information were downloaded from the public databases.

METHODS

Lipid metabolism pathways were collected from the MSigDB database, and molecular subtypes were classified based on lipid metabolism features via consensus clustering. The bidirectional crosstalk between immune cells and malignant cells was analyzed. Differences in lipid metabolism at the single-cell level and their correlation with the tumor microenvironment (TME) were also studied. LUAD patients were classified into two subtypes, showing distinct mutation and lipid metabolism features based on lipid metabolism characteristics. Meanwhile, significant differences in the overall survival, clinical characteristics, and immune landscape were observed between the two subtypes. We also found that clust1 had higher oxidative stress status. There were 116 differentially expressed genes between the two subtypes, which were significantly associated with cell cycle progression. We identified 4001 immune cells, including 483 malignant cells and 3518 normal cells, and found active intercellular communication and significant differences in lipid metabolism characteristics between the malignant cells and normal cells. Furthermore, several lipid metabolism pathways were found to be associated with TME factors, including hypoxia and angiogenesis.

RESULT

The current findings indicated that lipid metabolism was involved in the development and cellular heterogeneity of LUAD and revealed widespread reprogramming across multiple cellular elements in the TME of LUAD.

CONCLUSION

This characterization improved the current understanding of tumor biology and enabled the identification of novel targets for immunotherapy.

摘要

简介

脂质代谢在肺腺癌（LUAD）中的作用尚未完全研究清楚。脂质代谢重编程是恶性肿瘤的一个特征，有助于致癌和进展。从公共数据库下载了转录组和 scRNA-seq 数据及临床信息。

方法

从 MSigDB 数据库中收集脂质代谢途径，并根据脂质代谢特征通过共识聚类对分子亚型进行分类。分析免疫细胞和恶性细胞之间的双向串扰。还研究了单细胞水平的脂质代谢差异及其与肿瘤微环境（TME）的相关性。根据脂质代谢特征，将 LUAD 患者分为两个亚型，显示出明显不同的突变和脂质代谢特征。同时，两个亚型的总生存率、临床特征和免疫景观也存在显著差异。我们还发现 clust1 具有更高的氧化应激状态。两个亚型之间有 116 个差异表达基因，这些基因与细胞周期进展显著相关。我们鉴定了 4001 个免疫细胞，包括 483 个恶性细胞和 3518 个正常细胞，发现细胞间存在活跃的通讯，并且恶性细胞和正常细胞之间的脂质代谢特征存在显著差异。此外，还发现几个脂质代谢途径与 TME 因素有关，包括缺氧和血管生成。