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鉴定内质网应激相关基因作为结肠癌的预后标志物

Identification of endoplasmic reticulum stress-related genes as prognostic markers in colon cancer.

作者信息

Xu Wenjing, Li Wei, Kuai Dayu, Li Yaqiang, Sun Wei, Liu Xian, Xu Baohong

机构信息

Department of Gastroenterology, Beijing Luhe Hospital Affiliated to Capital Medical University, Beijing, China.

出版信息

Cancer Biol Ther. 2025 Dec;26(1):2458820. doi: 10.1080/15384047.2025.2458820. Epub 2025 Apr 1.

DOI:10.1080/15384047.2025.2458820
PMID:40169935
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11970746/
Abstract

Endoplasmic reticulum stress (ERS) has been implicated in the pathogenesis of various cancers, including colon cancer, by regulating tumor cell survival, growth, and immune response. However, the specific genes involved in ERS that could serve as prognostic markers in colon cancer remain underexplored. This study aims to identify and validate endoplasmic reticulum stress related genes (ERSRGs) in colon cancer that correlate with patient prognosis, thereby enhancing the understanding of ERS in oncological outcomes and potential therapeutic targeting. We utilized bioinformatics analyses to identify ERSRGs from publicly available colon cancer datasets. Differential expression analysis and survival analysis were performed to assess the prognostic significance of these genes. Validation was conducted through quantitative real-time PCR (RT-qPCR) on selected colon cancer cell lines. Our study identified nine ERS related genes (ASNS, ATF4, ATF6B, BOK, CLU, DDIT3, MANF, SLC39A14, TRAF2) involved in critical pathways including IL-12, PI3K-AKT, IL-7, and IL-23 signaling, and linked to 1-, 3-, and 5-year survival of patients with colon cancer. A multivariate Cox model based on these ERS related genes demonstrated significant prognostic power. Further, TRAF2 strong correlated with immune cells infiltration, suggesting its potential roles in modulating immune responses in the tumor microenvironment. The RT-qPCR validation confirmed the differential expression of these genes in human colon cancer cell lines versus human normal colonic epithelial cell line. The identified ERSRGs could serve as valuable prognostic markers and may offer new insights into the therapeutic targeting of ERS in colon cancer.

摘要

内质网应激（ERS）通过调节肿瘤细胞的存活、生长和免疫反应，参与了包括结肠癌在内的多种癌症的发病机制。然而，在结肠癌中，参与ERS且可作为预后标志物的特定基因仍未得到充分研究。本研究旨在识别和验证与结肠癌患者预后相关的内质网应激相关基因（ERSRGs），从而加深对ERS在肿瘤学结局及潜在治疗靶点方面的理解。我们利用生物信息学分析从公开的结肠癌数据集中识别ERSRGs。进行差异表达分析和生存分析以评估这些基因的预后意义。通过对选定的结肠癌细胞系进行定量实时PCR（RT-qPCR）来进行验证。我们的研究确定了9个与ERS相关的基因（ASNS、ATF4、ATF6B、BOK、CLU、DDIT3、MANF、SLC39A14、TRAF2），它们参与了包括IL-12、PI3K-AKT、IL-7和IL-23信号传导在内的关键通路，并与结肠癌患者的1年、3年和5年生存率相关。基于这些与ERS相关基因的多变量Cox模型显示出显著的预后能力。此外，TRAF2与免疫细胞浸润密切相关，表明其在调节肿瘤微环境中免疫反应方面的潜在作用。RT-qPCR验证证实了这些基因在人结肠癌细胞系与正常人结肠上皮细胞系中的差异表达。所确定的ERSRGs可作为有价值的预后标志物，并可能为结肠癌中ERS的治疗靶点提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/11970746/69dafdb2ed11/KCBT_A_2458820_F0013_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/11970746/b21055f21bc4/KCBT_A_2458820_F0009_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/11970746/91f9ee215d5a/KCBT_A_2458820_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/11970746/62b2639120d0/KCBT_A_2458820_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/11970746/ea1ef6f0e265/KCBT_A_2458820_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/11970746/b21055f21bc4/KCBT_A_2458820_F0009_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/11970746/55fd739c65ad/KCBT_A_2458820_F0010_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/11970746/4cc1495e6751/KCBT_A_2458820_F0011_OC.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ddd/11970746/69dafdb2ed11/KCBT_A_2458820_F0013_OC.jpg

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本文引用的文献

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An endoplasmic reticulum stress related signature for clinically predicting prognosis of breast cancer patients.一种用于临床预测乳腺癌患者预后的内质网应激相关特征。
Hum Mol Genet. 2024 Dec 4. doi: 10.1093/hmg/ddae170.
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Exploring Predictive and Prognostic Biomarkers in Colorectal Cancer: A Comprehensive Review.探索结直肠癌中的预测性和预后生物标志物：综述
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Construction of a prognostic model for colon cancer by combining endoplasmic reticulum stress responsive genes.
通过结合内质网应激反应基因构建结肠癌预后模型。
J Proteomics. 2024 Oct 30;309:105284. doi: 10.1016/j.jprot.2024.105284. Epub 2024 Aug 17.
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Identification and validation of endoplasmic reticulum stress-related genes that enhance immunotherapy in colon cancer.增强结肠癌免疫治疗的内质网应激相关基因的鉴定与验证
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Endoplasmic reticulum stress-a key guardian in cancer.内质网应激——癌症中的关键守护者。
Cell Death Discov. 2024 Jul 30;10(1):343. doi: 10.1038/s41420-024-02110-3.
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State-of-the-Art Management of Colorectal Cancer: Treatment Advances and Innovation.结直肠癌的最新治疗进展：治疗进展与创新。
Am Soc Clin Oncol Educ Book. 2024 Jun;44(3):e438466. doi: 10.1200/EDBK_438466.
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Recent Approaches on Molecular Markers, Treatment and Novel Drug Delivery System Used for the Management of Colorectal Cancer: A Comprehensive Review.近年来用于结直肠癌管理的分子标志物、治疗方法和新型药物传递系统的研究进展：综述
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