乳腺癌中 Anoikis 相关基因的预后价值和免疫特征

IF 3.2 4区 医学 Q3 IMMUNOLOGY Journal of Immunotherapy Pub Date : 2024-10-01 Epub Date: 2024-06-12 DOI:10.1097/CJI.0000000000000523
Qing Wu, Yang Luo, Nan Lin, Shiyao Zheng, Xianhe Xie
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引用次数: 0

摘要

从癌症基因组图谱(TCGA)和GSE42568数据库中获得了乳腺癌患者的转录组数据。然后,确定了乳腺癌相关基因(ANRGs),并构建了风险评分系统。以风险评分中位数作为阈值,将患者分为低风险组和高风险组。然后进行 Kaplan-Meier 分析,评估风险评分系统的预后能力,并使用 GSE7390 对其进行了验证。此外,我们还发现了模型中潜在的功能富集和肿瘤免疫浸润。最后,我们通过体外实验研究了风险基因(EPB41L4B)在乳腺癌中的生物学功能。我们通过9个预后ANRGs(CXCL2、EPB41L4B、SLC7A5、SFRP1、SDC1、BHLHE41、SPINT1、KRT15和CD24)构建了一个风险评分系统。Kaplan-Meier分析表明,TCGA-BRCA(训练集)和GSE7390(测试集)高危患者的生存结果都明显较差。此外,校准图与预后预测结果十分吻合。由于风险评分与ESTIMATE评分、肿瘤浸润淋巴细胞、免疫检查点和趋化因子呈负相关,因此可以利用风险组来筛选具有免疫抑制微环境的乳腺癌患者。此外,下调 EPB41L4B 基因的表达可抑制乳腺癌细胞的活力和迁移,并促进细胞凋亡。基于ANRGs,可以建立一个9基因预后模型来预测乳腺癌的预后;此外,高风险组患者处于免疫抑制的肿瘤微环境中。
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Prognostic Value and Immune Signatures of Anoikis-related Genes in Breast Cancer.

From databases of the Cancer Genome Atlas (TCGA) and GSE42568, transcriptome data of breast cancer patients was obtained. Then, anoikis-related genes (ANRGs) were identified and constructed a risk score system. As a threshold value, the median risk score was used to stratify patients into low-risk and high-risk groups. Kaplan-Meier analysis was then conducted to evaluate the prognostic ability of the risk score system, which was validated using GSE7390. Furthermore, we identified potential enrichment of function and tumor immune infiltration in the model. Finally, the biological functions of a risk gene (EPB41L4B) in breast cancer were investigated through in vitro experiments. We constructed a risk score system via 9 prognosis ANRGs (CXCL2, EPB41L4B, SLC7A5, SFRP1, SDC1, BHLHE41, SPINT1, KRT15, and CD24). The Kaplan-Meier analysis showed that both TCGA-BRCA (training set) and GSE7390 (testing set) patients with high-risk status had significantly worse survival outcomes. In addition, the calibration plots were in good agreement with the prognosis prediction. Breast cancer patients with immunosuppressive microenvironment could be screened using risk groups since risk scores were correlated negatively with ESTIMATE score, tumor-infiltration lymphocytes, immune checkpoints, and chemotactic factors. Furthermore, cellular viability and cell migration of cancerous breast cells were inhibited and apoptosis was promoted by down-regulation of EPB41L4B gene expression. Based on ANRGs, a 9-gene prognostic model could be developed to predict breast cancer prognosis; moreover, patients of the high-risk group were in an immunosuppressed tumor microenvironment.

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来源期刊
Journal of Immunotherapy
Journal of Immunotherapy 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
79
审稿时长
6-12 weeks
期刊介绍: Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.
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