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肺腺癌免疫相关代谢基因的综合分析。

Comprehensive Analysis of Immune-Related Metabolic Genes in Lung Adenocarcinoma.

机构信息

Department of Respiratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Endocrinol (Lausanne). 2022 Jul 8;13:894754. doi: 10.3389/fendo.2022.894754. eCollection 2022.

DOI:10.3389/fendo.2022.894754
PMID:35898471
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9309246/
Abstract

PURPOSE

The immunotherapy of lung adenocarcinoma (LUAD) has received much attention in recent years and metabolic reprogramming is linked to immune infiltration in the tumor microenvironment. Therefore, it is indispensable to dissect the role of immune-related metabolic genes in lung adenocarcinoma.

METHODS

In this study, we screened immune-related genes by Pearson correlation. The function of these genes was explored by gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. The differently expressed immune-related genes were analyzed by Limma. Furthermore, the LUAD patients were clustered based on immune-related genes through consensus clustering. The Unicox was used to identify survival-immune-related metabolic genes. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to optimize the gene sets. A prediction model was constructed and tested. The potential therapeutic target was selected based on two criteria, these immune-related metabolic genes that were highly expressed in tumor tissues and negatively correlated with the survival of patients in LUAD. Quantitative real-time PCR (qRT-PCR) was used for experimental validations.

RESULTS

We identified 346 immune-related genes, mainly involved in arachidonic acid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling. Moreover, a total of 141 immune-related genes were dysregulated between tumor and normal tissues. We clustered three subtypes of LUAD based on immune-related metabolic genes and these subtypes exhibited different survival and immune status. We found Ribonucleotide Reductase Regulatory Subunit M2 () as a potential therapeutic target, which is positively correlated with the cyclin-dependent kinase family of genes.

CONCLUSION

We comprehensively analyzed the immune-related metabolic genes in LUAD. was determined as a promising metabolic checkpoint for lung adenocarcinoma.

摘要

目的

近年来，肺腺癌（LUAD）的免疫治疗受到了广泛关注，代谢重编程与肿瘤微环境中的免疫浸润有关。因此，剖析免疫相关代谢基因在肺腺癌中的作用是必不可少的。

方法

在本研究中，我们通过 Pearson 相关性筛选免疫相关基因。通过基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析探讨这些基因的功能。通过 Limma 分析差异表达的免疫相关基因。此外，根据免疫相关基因对 LUAD 患者进行共识聚类。使用 Unicox 识别与生存相关的免疫代谢基因。使用最小绝对收缩和选择算子（LASSO）回归分析优化基因集。构建并测试预测模型。选择基于两个标准的潜在治疗靶点，这些在肿瘤组织中高表达且与 LUAD 患者生存呈负相关的免疫相关代谢基因。采用实时定量 PCR（qRT-PCR）进行实验验证。

结果

我们鉴定了 346 个免疫相关基因，主要涉及花生四烯酸代谢和过氧化物酶体增殖物激活受体（PPAR）信号通路。此外，肿瘤组织和正常组织之间共有 141 个免疫相关基因失调。我们根据免疫相关代谢基因将 LUAD 聚类为三个亚型，这些亚型表现出不同的生存和免疫状态。我们发现核苷酸还原酶调节亚基 M2（）是一个有前途的治疗靶点，它与细胞周期蛋白依赖性激酶家族基因呈正相关。

结论

我们全面分析了 LUAD 中的免疫相关代谢基因。确定为肺腺癌有希望的代谢检查点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/8ca2b746e503/fendo-13-894754-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/bc18b0dbf033/fendo-13-894754-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/9659b57189e7/fendo-13-894754-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/8977a75789c3/fendo-13-894754-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/269ee9a79a17/fendo-13-894754-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/8ca2b746e503/fendo-13-894754-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/bc18b0dbf033/fendo-13-894754-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/6a1d1bd6c45d/fendo-13-894754-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/9659b57189e7/fendo-13-894754-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/561ebe6031eb/fendo-13-894754-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/8977a75789c3/fendo-13-894754-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/269ee9a79a17/fendo-13-894754-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0f38/9309246/8ca2b746e503/fendo-13-894754-g007.jpg

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