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鉴定和验证色氨酸相关基因特征，以预测肺腺癌的预后和免疫治疗反应，揭示了 PTTG1 的关键作用。

Identification and validation of tryptophan-related gene signatures to predict prognosis and immunotherapy response in lung adenocarcinoma reveals a critical role for PTTG1.

机构信息

Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Joint Research Center for Regional Diseases of Institute of Health and Medicine (IHM), First Affiliated Hospital of Bengbu Medical University, Bengbu, China.

Research Center of Clinical Laboratory Science, Bengbu Medical University, Bengbu, China.

出版信息

Front Immunol. 2024 Jul 31;15:1386427. doi: 10.3389/fimmu.2024.1386427. eCollection 2024.

DOI:10.3389/fimmu.2024.1386427
PMID:39144144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11321965/
Abstract

INTRODUCTION: Tryptophan metabolism is strongly associated with immunosuppression and may influence lung adenocarcinoma prognosis as well as tumor microenvironment alterations. METHODS: Sequencing datasets were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Two different clusters were identified by consensus clustering, and prognostic models were established based on differentially expressed genes (DEGs) in the two clusters. We investigated differences in mutational landscapes, enrichment pathways, immune cell infiltration, and immunotherapy between high- and low-risk scoring groups. Single-cell sequencing data from Bischoff et al. were used to identify and quantify tryptophan metabolism, and model genes were comprehensively analyzed. Finally, PTTG1 was analyzed at the pan-cancer level by the pan-TCGA cohort. RESULTS: Risk score was defined as an independent prognostic factor for lung adenocarcinoma and was effective in predicting immunotherapy response in patients with lung adenocarcinoma. PTTG1 is one of the key genes, and knockdown of PTTG1 decreases lung adenocarcinoma cell proliferation and migration and promotes apoptosis and down-regulation of tryptophan metabolism regulators in lung adenocarcinoma cells. DISCUSSION: Our study revealed the pattern and molecular features of tryptophan metabolism in lung adenocarcinoma patients, established a model of tryptophan metabolism-associated lung adenocarcinoma prognosis, and explored the roles of PTTG1 in lung adenocarcinoma progression, EMT process, and tryptophan metabolism.

摘要

简介：色氨酸代谢与免疫抑制密切相关，可能影响肺腺癌的预后以及肿瘤微环境的改变。 方法：从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）中获取测序数据集。通过共识聚类确定了两个不同的聚类，根据两个聚类中差异表达基因（DEGs）建立了预后模型。我们研究了高风险和低风险评分组之间突变景观、富集途径、免疫细胞浸润和免疫治疗的差异。使用 Bischoff 等人的单细胞测序数据来识别和量化色氨酸代谢，并对模型基因进行全面分析。最后，通过泛 TCGA 队列分析 PTTG1 在泛癌水平上的表达。 结果：风险评分被定义为肺腺癌的独立预后因素，可有效预测肺腺癌患者的免疫治疗反应。PTTG1 是关键基因之一，敲低 PTTG1 可降低肺腺癌细胞的增殖和迁移，促进肺腺癌细胞的凋亡和色氨酸代谢调节因子的下调。 讨论：本研究揭示了肺腺癌患者色氨酸代谢的模式和分子特征，建立了色氨酸代谢相关肺腺癌预后模型，并探讨了 PTTG1 在肺腺癌进展、EMT 过程和色氨酸代谢中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5139/11321965/eb2343d5634a/fimmu-15-1386427-g014.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5139/11321965/4377bd676d24/fimmu-15-1386427-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5139/11321965/24d5660056b4/fimmu-15-1386427-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5139/11321965/eb2343d5634a/fimmu-15-1386427-g014.jpg

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本文引用的文献

[1]
Purine metabolism in lung adenocarcinoma: A single-cell analysis revealing prognostic and immunotherapeutic insights.

J Cell Mol Med. 2024-4

[2]
Identification and Verification of Metabolism-related Immunotherapy Features and Prognosis in Lung Adenocarcinoma.

Curr Med Chem. 2025

[3]
Deciphering Treg cell roles in esophageal squamous cell carcinoma: a comprehensive prognostic and immunotherapeutic analysis.

Front Mol Biosci. 2023-9-28

[4]
The integrated single-cell analysis developed an immunogenic cell death signature to predict lung adenocarcinoma prognosis and immunotherapy.

Aging (Albany NY). 2023-10-4

[5]
Predicting lung adenocarcinoma prognosis, immune escape, and pharmacomic profile from arginine and proline-related genes.

Sci Rep. 2023-9-14

[6]
PTTG1 Reprograms Asparagine Metabolism to Promote Hepatocellular Carcinoma Progression.

Cancer Res. 2023-7-14

[7]
Identification of natural killer cell associated subtyping and gene signature to predict prognosis and drug sensitivity of lung adenocarcinoma.

Front Genet. 2023-4-7

[8]
Lung cancer immunotherapy: progress, pitfalls, and promises.

Mol Cancer. 2023-2-21

[9]
By integrating single-cell RNA-seq and bulk RNA-seq in sphingolipid metabolism, CACYBP was identified as a potential therapeutic target in lung adenocarcinoma.

Front Immunol. 2023

[10]
A Metabolism-Related Gene Prognostic Index for Prediction of Response to Immunotherapy in Lung Adenocarcinoma.

Int J Mol Sci. 2022-10-12

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