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鉴定 TUBB2A 为三阴性乳腺癌中癌症免疫循环相关的治疗靶点。

Identification of TUBB2A as a Cancer-Immunity Cycle-Related Therapeutic Target in Triple-Negative Breast Cancer.

机构信息

Department of Breast Surgical Oncology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Xinghualing District, Taiyuan, 030013, Shanxi Province, People's Republic of China.

Department of Head and Neck, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Xinghualing District, Taiyuan, 030013, Shanxi Province, People's Republic of China.

出版信息

Mol Biotechnol. 2024 Sep;66(9):2467-2480. doi: 10.1007/s12033-023-00880-2. Epub 2023 Sep 24.

DOI:10.1007/s12033-023-00880-2
PMID:37742297
Abstract

OBJECTIVE

Triple negative breast cancer (TNBC) is a malignant subtype of breast cancer characterized by the absence of ER, PR, and HER2. We aimed to explore target gene from the perspective of cancer-immunity cycle, providing insights into treatment of TNBC.

METHODS

We obtained TNBC samples from METABRIC database and downloaded 4 datasets from GEO database, as well as an IMvigor210 dataset. WGCNA was applied to screen genes associated with cancer-immunity cycle in TNBC. GO, KEGG and GSEA analyses were performed to explore the target gene's potential functions and pathways. The binding motifs with transcription factors were predicted with FIMO. Immune infiltration analysis was conducted by CIBERSORT.

RESULTS

TUBB2A was screened out as our target gene which was negatively correlated with T cell recruitment in cancer-immunity cycle. TUBB2A expressed higher in TNBC samples than in normal samples. High expression of TUBB2A was associated with poor prognosis of TNBC. 12 transcription factors and 5 miRNAs might regulate TUBB2A's expression. The infiltration ratios of 7 types of immune cells such as CD8 T cells, naive CD4 T cells and activated memory CD4 T cells were significantly lower in TUBB2A high expression group. TUBB2A was a potential drug target.

CONCLUSION

We screened a cancer-immunity cycle-related gene TUBB2A which was negatively correlated with T cell recruiting in TNBC. TUBB2A expressed higher in TNBC samples than in normal samples, associated with poor prognosis.

摘要

目的

三阴性乳腺癌(TNBC)是一种恶性乳腺癌亚型,其特征是缺乏 ER、PR 和 HER2。我们旨在从癌症免疫循环的角度探索靶基因,为 TNBC 的治疗提供思路。

方法

我们从 METABRIC 数据库中获取 TNBC 样本,并从 GEO 数据库下载了 4 个数据集,以及一个 IMvigor210 数据集。我们应用 WGCNA 筛选与 TNBC 癌症免疫循环相关的基因。进行 GO、KEGG 和 GSEA 分析,以探讨靶基因的潜在功能和途径。使用 FIMO 预测与转录因子结合的基序。通过 CIBERSORT 进行免疫浸润分析。

结果

筛选出与癌症免疫循环中 T 细胞募集呈负相关的靶基因 TUBB2A。TUBB2A 在 TNBC 样本中的表达高于正常样本。TUBB2A 高表达与 TNBC 的不良预后相关。12 个转录因子和 5 个 miRNA 可能调节 TUBB2A 的表达。TUBB2A 高表达组中 7 种免疫细胞(如 CD8 T 细胞、幼稚 CD4 T 细胞和激活记忆 CD4 T 细胞)的浸润比例明显较低。TUBB2A 是一个潜在的药物靶点。

结论

我们筛选出与 TNBC 中 T 细胞募集呈负相关的癌症免疫循环相关基因 TUBB2A。TUBB2A 在 TNBC 样本中的表达高于正常样本,与不良预后相关。

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