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构建一种新型线粒体代谢相关基因特征以评估肿瘤免疫微环境并预测结直肠癌患者的生存情况。

Constructing a novel mitochondrial metabolism-related genes signature to evaluate tumor immune microenvironment and predict survival of colorectal cancer.

作者信息

Wang Hou, Zhang Kai, Ning Guang

机构信息

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai National Clinical Research Center for Metabolic Diseases, Shanghai National Center for Translational Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Med (Lausanne). 2025 Jul 8;12:1618471. doi: 10.3389/fmed.2025.1618471. eCollection 2025.

DOI:10.3389/fmed.2025.1618471
PMID:40697926
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12279720/
Abstract

BACKGROUND: Colorectal cancer (CRC) is a highly lethal gastrointestinal malignancy with substantial global health implications. Although mitochondrial metabolism genes play a crucial role in CRC development, their prognostic significance remains unclear. METHODS: This study systematically analyzed the expression and prognostic value of mitochondrial metabolism-related genes in CRC patients, establishing a risk model using data from TCGA and GEO databases. We also investigated the tumor microenvironment (TME), immune cell infiltration, tumor mutation burden, microsatellite instability (MSI), and drug sensitivity. Core mitochondrial metabolism-related gene, TMEM86B was identified and its functions validated through cell-based assays and mouse models. RESULTS: Fifteen mitochondrial metabolism-related genes were identified, including HSD3B7, ORC1, GPSM2, NDUFA4L2, CHDH, LARS2, TMEM86B, FABP4, TNFAIP8L3, HMGCL, GDE1, ACOX1, ARV1, HDC, and GSR. The nomogram, which incorporates independent prognostic genes TMEM86B, TNFAIP8L3, HDC, and key clinical features pTNM stage (pathological Tumor-Node-Metastasis), age, was created to predict patient outcomes. Notable differences in immune cell infiltration were observed between risk groups. The risk score was associated with TME genes and immune checkpoints, indicating an immunosuppressive environment in high-risk groups. Furthermore, TIDE analysis revealed that integrating the risk score with immune score, stromal score, or microsatellite status improved the prediction of immunotherapy response across different CRC patient subgroups. Core mitochondrial metabolism-related gene, TMEM86B promotes colorectal cancer progression by enhancing cell proliferation, migration, and invasion, and its downregulation significantly inhibits tumor growth both and . CONCLUSION: Our findings indicate that the risk model associated with mitochondrial metabolism may serve as a dependable prognostic indicator, facilitating tailored therapeutic strategies for CRC patients. TMEM86B promotes colorectal cancer progression, and its downregulation inhibits tumor growth and .

摘要

背景：结直肠癌（CRC）是一种具有高度致死性的胃肠道恶性肿瘤，对全球健康有着重大影响。尽管线粒体代谢基因在CRC发展中起着关键作用，但其预后意义仍不明确。 方法：本研究系统分析了CRC患者中线粒体代谢相关基因的表达及预后价值，利用来自TCGA和GEO数据库的数据建立了一个风险模型。我们还研究了肿瘤微环境（TME）、免疫细胞浸润、肿瘤突变负荷、微卫星不稳定性（MSI）和药物敏感性。鉴定了核心线粒体代谢相关基因TMEM86B，并通过细胞实验和小鼠模型验证了其功能。 结果：鉴定出15个线粒体代谢相关基因，包括HSD3B7、ORC1、GPSM2、NDUFA4L2、CHDH、LARS2、TMEM86B、FABP4、TNFAIP8L3、HMGCL、GDE1、ACOX1、ARV1、HDC和GSR。创建了包含独立预后基因TMEM86B、TNFAIP8L3、HDC以及关键临床特征pTNM分期（病理肿瘤-淋巴结-转移）、年龄的列线图，以预测患者预后。在风险组之间观察到免疫细胞浸润存在显著差异。风险评分与TME基因和免疫检查点相关，表明高危组存在免疫抑制环境。此外，TIDE分析显示，将风险评分与免疫评分、基质评分或微卫星状态相结合，可改善对不同CRC患者亚组免疫治疗反应的预测。核心线粒体代谢相关基因TMEM86B通过增强细胞增殖、迁移和侵袭促进结直肠癌进展，其下调显著抑制肿瘤生长。 结论：我们的研究结果表明，与线粒体代谢相关的风险模型可能作为一个可靠的预后指标，为CRC患者制定个性化治疗策略提供便利。TMEM86B促进结直肠癌进展，其下调抑制肿瘤生长。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d679/12279720/f6faf173e231/fmed-12-1618471-g011.jpg
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本文引用的文献

[1]
Immune gene features and prognosis in colorectal cancer: insights from ssGSEA typing.

Discov Oncol. 2025-2-8

[2]
Machine learning-based model for CD4 conventional T cell genes to predict survival and immune responses in colorectal cancer.

Sci Rep. 2024-10-18

[3]
Spatial transcriptome and single-cell reveal the role of nucleotide metabolism in colorectal cancer progression and tumor microenvironment.

J Transl Med. 2024-7-29

[4]
Novel hypoxia- and lactate metabolism-related molecular subtyping and prognostic signature for colorectal cancer.

J Transl Med. 2024-6-20

[5]
Down-regulated expression of TIPE3 inhibits malignant progression of non-small cell lung cancer via Wnt signaling.

Exp Cell Res. 2024-6-15

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G-Protein Signaling Modulator 2 as a Potential Biomarker in Colorectal Cancer: Integrative Analysis Using Genetic Profiling and Pan-Cancer Studies.

Genes (Basel). 2024-4-9

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Construction and Analysis of a Mitochondrial Metabolism-Related Prognostic Model for Breast Cancer to Evaluate Survival and Immunotherapy.

J Membr Biol. 2024-4

[9]
A Treg-related riskscore model may improve the prognosis evaluation of colorectal cancer.

J Gene Med. 2024-2

[10]
Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer.

Open Med (Wars). 2023-11-9

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