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机器学习揭示了两种基于肺腺癌脂质代谢的异质亚型，以辅助免疫治疗。

Machine learning reveals two heterogeneous subtypes to assist immune therapy based on lipid metabolism in lung adenocarcinoma.

机构信息

School of Medicine, Southeast University, Nanjing, China.

Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.

出版信息

Front Immunol. 2022 Sep 27;13:1022149. doi: 10.3389/fimmu.2022.1022149. eCollection 2022.

DOI:10.3389/fimmu.2022.1022149
PMID:36238302
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9551187/
Abstract

BACKGROUND: Lipid metabolism pivotally contributes to the incidence and development of lung adenocarcinoma (LUAD). The interaction of lipid metabolism and tumor microenvironment (TME) has become a new research direction. METHODS: Using the 1107 LUAD records from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, a comprehensive exploration was performed on the heterogeneous lipid metabolism subtypes based on lipid metabolism genes (LMGs) and immune-related genes (LRGs). The clinical significance, functional status, TME interaction and genomic changes of different subtypes were further studied. A new scoring system, lipid-immune score (LIS), was developed and validated. RESULTS: Two heterogeneous subtypes, which express more LMGs and show the characteristics of tumor metabolism and proliferation, are defined as lipid metabolism phenotypes. The prognosis of lipid metabolism phenotype is poor, and it is more common in patients with tumor progression. Expressing more IRGs, enrichment of immunoactive pathways and infiltration of effector immune cells are defined as immunoactive phenotypes. The immunoactive phenotype has a better prognosis and stronger anti-tumor immunity and is more sensitive to immunotherapy. In addition, KEAP1 is a driving mutant gene in the lipid metabolism subtype. Finally, LIS was developed and confirmed to be a robust predictor of overall survival (OS) and immunotherapy in LUAD patients. CONCLUSION: Two heterogeneous subtypes of LUAD (lipid metabolism subtype and immune activity subtype) were identified to evaluate prognosis and immunotherapy sensitivity. Our research promotes the understanding of the interaction between lipid metabolism and TME and offers a novel direction for clinical management and precision therapy aimed to LUAD patients.

摘要

背景：脂质代谢对肺腺癌（LUAD）的发生和发展起着关键作用。脂质代谢与肿瘤微环境（TME）的相互作用已成为一个新的研究方向。

方法：利用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中的 1107 例 LUAD 记录，基于脂质代谢基因（LMGs）和免疫相关基因（LRGs），对异质性脂质代谢亚型进行了全面探索。进一步研究了不同亚型的临床意义、功能状态、TME 相互作用和基因组变化。建立并验证了一种新的评分系统，即脂质免疫评分（LIS）。

结果：两种异质性亚型，表达更多的 LMGs，表现出肿瘤代谢和增殖的特征，被定义为脂质代谢表型。脂质代谢表型的预后较差，在肿瘤进展患者中更为常见。表达更多的 IRGs、免疫活性途径的富集和效应免疫细胞的浸润被定义为免疫活性表型。免疫活性表型的预后较好，具有更强的抗肿瘤免疫能力，对免疫治疗更敏感。此外，KEAP1 是脂质代谢亚型中的驱动突变基因。最后，建立并验证了 LIS 是 LUAD 患者总生存期（OS）和免疫治疗的强有力预测因子。

结论：鉴定出两种异质性 LUAD 亚型（脂质代谢亚型和免疫活性亚型），以评估预后和免疫治疗敏感性。我们的研究促进了对脂质代谢与 TME 相互作用的理解，为 LUAD 患者的临床管理和精准治疗提供了新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/5c5783bd12b4/fimmu-13-1022149-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/d62871eb531b/fimmu-13-1022149-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/fa291d2fd540/fimmu-13-1022149-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/bcb2f59cca45/fimmu-13-1022149-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/dc27b5184f4f/fimmu-13-1022149-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/d0b1c660f4cf/fimmu-13-1022149-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/1f37bbcfa07a/fimmu-13-1022149-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/fec6c3a585b1/fimmu-13-1022149-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/13383c224037/fimmu-13-1022149-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/5c5783bd12b4/fimmu-13-1022149-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/d62871eb531b/fimmu-13-1022149-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/fa291d2fd540/fimmu-13-1022149-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/bcb2f59cca45/fimmu-13-1022149-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/dc27b5184f4f/fimmu-13-1022149-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/d0b1c660f4cf/fimmu-13-1022149-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/1f37bbcfa07a/fimmu-13-1022149-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/fec6c3a585b1/fimmu-13-1022149-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/13383c224037/fimmu-13-1022149-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed01/9551187/5c5783bd12b4/fimmu-13-1022149-g009.jpg

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本文引用的文献

[1]
Integratively Genomic Analysis Reveals the Prognostic and Immunological Characteristics of Pyroptosis and Ferroptosis in Pancreatic Cancer for Precision Immunotherapy.

Front Cell Dev Biol. 2022-2-15

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Front Immunol. 2021

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Front Oncol. 2021-10-22

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