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基于14个缺氧相关基因鉴定结肠癌缺氧相关特征以评估肿瘤免疫微环境并预测预后

Identification of Hypoxia-Associated Signature in Colon Cancer to Assess Tumor Immune Microenvironment and Predict Prognosis Based on 14 Hypoxia-Associated Genes.

作者信息

Chen Peng, Li Zhongxin, Liang Yulong, Wei Ming, Jiang Haibo, Chen Shihao, Zhao Zengren

机构信息

Department of General Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People's Republic of China.

Department of General Surgery, The First Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People's Republic of China.

出版信息

Int J Gen Med. 2023 Jun 16;16:2503-2518. doi: 10.2147/IJGM.S407005. eCollection 2023.

Abstract

PURPOSE

Colon cancer is the main malignant tumor of the digestive tract. Hypoxia is highly related to the occurrence, progression and tumor immune microenvironment (TIME) of cancer. The aim of this study was to identify a hypoxia-associated signature with high accuracy for predicting the prognosis and TIME of colon cancer.

METHODS

Download colon cancer data from the GEO and TCGA databases. A novel hypoxia risk model was identified to predict the prognosis of colon cancer patients. Subsequently, GSEA, TIME and mutation analysis were performed in the hypoxia high and low risk score groups. Finally, the signature gene ANKZF1 was selected for functional verification at the cellular level.

RESULTS

A novel hypoxia risk model was identified. The risk score was significantly associated with poorer overall survival in colon cancer, and could be used as an independent prognostic factor for colon cancer. GSEA analysis found that the processes related to stimulate tumor proliferation and anti-apoptosis were significantly enriched in the hypoxia high risk score group. The expression of immunosuppressive cells and most immune checkpoints in the high risk score group was significantly higher than that in the low risk score group. In vitro cell experiments showed that knockdown the expression of ANKZF1 could inhibit the proliferation, migration and invasion of colon cancer cells.

CONCLUSION

Hypoxia plays an important role in evaluating the TIME and predicting the prognosis of colon cancer.

摘要

目的

结肠癌是消化道主要恶性肿瘤。缺氧与癌症的发生、进展及肿瘤免疫微环境(TIME)高度相关。本研究旨在精准识别一种与缺氧相关的特征,用于预测结肠癌的预后及TIME。

方法

从GEO和TCGA数据库下载结肠癌数据。鉴定出一种新型缺氧风险模型以预测结肠癌患者的预后。随后,在缺氧高风险和低风险评分组中进行基因集富集分析(GSEA)、TIME及突变分析。最后,选择特征基因ANKZF1在细胞水平进行功能验证。

结果

鉴定出一种新型缺氧风险模型。风险评分与结肠癌患者较差的总生存期显著相关,且可作为结肠癌的独立预后因素。GSEA分析发现,与刺激肿瘤增殖和抗凋亡相关的过程在缺氧高风险评分组中显著富集。高风险评分组中免疫抑制细胞和大多数免疫检查点的表达显著高于低风险评分组。体外细胞实验表明,敲低ANKZF1的表达可抑制结肠癌细胞的增殖、迁移和侵袭。

结论

缺氧在评估结肠癌的TIME及预测预后中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/beb1/10281280/e6b3a1b52590/IJGM-16-2503-g0001.jpg

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