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Abstract：
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.
摘要：
乳腺癌仍然是女性癌症相关死亡的主要原因，三阳性乳腺癌（TPBC）是一种特别侵袭性的亚型。GATA结合蛋白3(GATA3)在乳腺上皮细胞腔分化和T细胞分化中起着至关重要的作用。然而,TPBC中GATA3与免疫浸润之间的关系尚不清楚。本研究收集并分析了来自癌症基因组图谱（TCGA）的TPBC数据，金属,和GSE123845数据库。单变量和多变量Cox回归分析，连同Kaplan-Meier生存分析，用于评估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）以探讨TPBC中GATA3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,临床样本用于检测GATA3表达与肿瘤浸润淋巴细胞（TIL）水平之间的关系。我们的结果表明，与正常组织相比，GATA3在TPBC组织中明显过表达（P<0.05）。GATA3mRNA与蛋白水平呈正相关(R=0.55,P<0.05)。值得注意的是,高GATA3表达与低总生存率相关(HR=1.24,95%置信区间(CI)1.25-11.76,P<0.05)。GSEA表明在低GATA3表达组中免疫相关基因集显著富集。此外，与残留疾病（RD）患者相比，病理完全缓解（pCR）患者的GATA3表达显着降低。突变分析显示高GATA3表达组中PIK3CA和TP53突变率较高。最后,临床验证数据显示，GATA3低表达组TILs程度显著增高。总之,本研究提示GATA3高表达可能与预后不良相关,并可能减少TPBC的免疫浸润.
