Zhang Zeyu, Qiu Xiangyuan, Yan Yuanliang, Liang Qiujiu, Cai Yuan, Peng Bi, Xu Zhijie, Xia Fada
Department of Thyroid Surgery, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Int J Gen Med. 2021 Sep 28;14:6189-6200. doi: 10.2147/IJGM.S329031. eCollection 2021.
Ferroptosis is the latest-discovered, iron-dependent form of regulated cell death. It has been increasingly recognized that ferroptosis-related genes participate in oncogenesis and development of cancers, including breast cancer (). Thus, It is important to explore the biofunctions of ferroptosis-related genes in .
Transcriptome microarray datasets (GSE22358, GSE9014 and GSE8977, GSE2990 and GSE2034) and TCGA- were retrieved for analyses. And a variety of computational tools were used to identify the roles and associated biological functions in .
Two ferroptosis-related genes ( and ) were significantly expressed in GSE22358, GSE9014 and GSE8977. Higher expression of was related with favorable prognosis. TCGA- further confirmed the expression of and the prognostic value of . Co-expression analyses showed the most enriched GO term and KEGG pathways were termination of DNA-templated transcription and Fanconi anemia pathway. Subsequently, immunological analyses showed was significantly associated with various immune infiltration cells; among these, dendritic cells, neutrophils, macrophages were the top three infiltrating cells. Furthermore, was also associated with multiple immunostimulatory molecules and chemokines, including PD-1, PD-L1, CTLA4, B7-H3, VSIR, IL-6, BTLA, CXCL2, and CCR7. These results indicated the potential roles of in the immune reaction during the pathogenesis of breast cancer.
This study firstly demonstrated that ferroptosis-related gene, , could be associated with immune microenvironment, thereby influencing the development and prognosis of patient with breast cancer.
铁死亡是最新发现的、铁依赖性的程序性细胞死亡形式。人们越来越认识到,铁死亡相关基因参与包括乳腺癌在内的癌症的发生和发展。因此,探索铁死亡相关基因在乳腺癌中的生物学功能具有重要意义。
检索转录组微阵列数据集(GSE22358、GSE9014、GSE8977、GSE2990和GSE2034)以及TCGA数据库进行分析。并使用多种计算工具来确定其在乳腺癌中的作用和相关生物学功能。
两个铁死亡相关基因(和)在GSE22358、GSE9014和GSE8977中显著表达。较高的表达与良好的预后相关。TCGA数据库进一步证实了的表达及其预后价值。共表达分析显示,最富集的基因本体(GO)术语和京都基因与基因组百科全书(KEGG)通路是DNA模板转录终止和范可尼贫血通路。随后,免疫分析显示与多种免疫浸润细胞显著相关;其中,树突状细胞、中性粒细胞、巨噬细胞是浸润最多的三种细胞。此外,还与多种免疫刺激分子和趋化因子相关,包括程序性死亡受体1(PD-1)、程序性死亡配体1(PD-L1)、细胞毒性T淋巴细胞相关蛋白4(CTLA4)、B7-H3、病毒抑制因子(VSIR)、白细胞介素6(IL-6)、B和T淋巴细胞衰减蛋白(BTLA)、CXC趋化因子配体2(CXCL2)和C-C趋化因子受体7(CCR7)。这些结果表明在乳腺癌发病机制的免疫反应中具有潜在作用。
本研究首次证明,铁死亡相关基因可与免疫微环境相关,从而影响乳腺癌患者的病情发展和预后。