基于 DNA 超分子水凝胶的保护性 NK 细胞储库用于增强三阴性乳腺癌治疗
Protective NK Cell Reservoir Based on DNA Supramolecular Hydrogel for Enhanced Triple-Negative Breast Cancer Therapy.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
三阳性乳腺癌中 GATA3 表达与总生存期和免疫细胞浸润的关联
英文原题：Association of GATA3 expression in triple-positive breast cancer with overall survival and immune cell infiltration.
查看英文原题
Association of GATA3 expression in triple-positive breast cancer with overall survival and immune cell infiltration.
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中文摘要
乳腺癌仍然是女性癌症相关死亡的主要原因之一，其中三阳性乳腺癌（TPBC）是一种特别具有侵袭性的亚型。GATA结合蛋白3（GATA3）在乳腺上皮的管腔分化和T细胞分化中起着至关重要的作用。
然而，GATA3与TPBC中免疫浸润之间的关系仍不清楚。本研究从The Cancer Genome Atlas（TCGA）、METABRIC和GSE123845数据库中收集并分析了TPBC数据。采用单因素和多因素Cox回归分析以及Kaplan-Meier生存分析评估GATA3和其他临床特征的预后价值。随后，进行基因集富集分析（GSEA）以探索GATA3在TPBC中的潜在生物学功能和调控机制。
此外，ssGSEA分析揭示了GATA3与免疫浸润之间的联系。并探讨了新辅助化疗和免疫治疗对GATA3表达的影响。最后，使用临床样本检测GATA3表达与TIL（肿瘤浸润淋巴细胞）水平之间的关系。
我们的结果表明，与正常组织相比，GATA3在TPBC组织中显著过表达（P < 0.05）。观察到GATA3 mRNA与蛋白水平之间呈正相关（R = 0.55，P < 0.05）。
值得注意的是，高GATA3表达与较差的总生存期相关（HR = 1.24，95%置信区间（CI）1.25-11.76，P < 0.05）。GSEA表明免疫相关基因集在低GATA3表达组中显著富集。
此外，病理完全缓解（pCR）患者的GATA3表达显著低于残留病灶（RD）患者。突变分析显示，GATA3高表达组的PIK3CA和TP53突变率更高。
最后，临床验证数据显示，GATA3低表达组的TILs程度显著更高。总之，本研究表明，GATA3高表达可能与TPBC的不良预后相关，并可能降低免疫浸润。
展开英文摘要原文
Breast cancer remains a leading cause of cancer-related mortality among women, with triple-positive breast cancer (TPBC) being a particularly aggressive subtype. GATA binding protein 3 (GATA3) plays a crucial role in the luminal differentiation of breast epithelium and T-cell differentiation.
However, the relationship between GATA3 and immune infiltration in TPBC remains unclear.
This study collected and analyzed TPBC data from The Cancer Genome Atlas (TCGA), METABRIC, and GSE123845 databases. Univariate and multivariate Cox regression analyses, along with Kaplan-Meier survival analyses, were employed to assess the prognostic value of GATA3 and other clinical features. Subsequently, Gene Set Enrichment Analysis (GSEA) was conducted to explore the potential biological functions and regulatory mechanisms of GATA3 in TPBC.
Additionally, ssGSEA analysis revealed the connection between GATA3 and immune infiltration. And the effects of neoadjuvant chemotherapy and immunotherapy on GATA3 expression were also explored.
Finally, clinical samples were used to detect the relationship between GATA3 expression and tumor infiltrating lymphocyte (TIL) levels.
Our results demonstrated that GATA3 was significantly overexpressed in TPBC tissues compared to normal tissues (P < 0. 05). A positive correlation between GATA3 mRNA and protein levels was observed (R = 0. 55, P < 0. 05).
Notably, high GATA3 expression was associated with poor overall survival (HR = 1. 24, 95% confidence interval (CI) 1. 25-11. 76, P < 0. 05). GSEA indicated significant enrichment of immune-related gene sets in low GATA3 expression groups.
Furthermore, pathologic complete response (pCR) patients exhibited significantly lower GATA3 expression compared to residual disease (RD) patients. Mutation analysis revealed higher PIK3CA and TP53 mutation rates in high GATA3 expression groups. Finally, clinical validation data showed that the degree of TILs was significantly higher in the low GATA3 expression group. In conclusion, this study suggests that high GATA3 expression may be associated with poor prognosis and may reduce immune infiltration in TPBC.
论文信息
- 作者
- Chen X、Zhao W、Huang Y、Luo S、Tang X、Yi Q
- 第一作者单位
- Department of Pathology and Department of Hematology, Taihe Hospital, Hubei University of Medicine, Hubei, China.China
- 通讯作者单位
- Department of Pathology and Department of Hematology, Taihe Hospital, Hubei University of Medicine, Hubei, China. yiqiong0428@163.com.China
- 期刊
- Scientific reports2024 Aug 1
- 原文标识
- PubMed 39090342 · DOI 10.1038/s41598-024-68788-8
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