Yi Jiarong, Zhong Wenjing, Wu Haoming, Feng Jikun, Zouxu Xiazi, Huang Xinjian, Li Siqi, Shuang Zeyu
Department of Breast Oncology, Sun Yat-sen University Cancer Center, The State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Front Oncol. 2021 Oct 21;11:746058. doi: 10.3389/fonc.2021.746058. eCollection 2021.
Although the tumor microenvironment (TME) plays an important role in the development of many cancers, its roles in breast cancer, especially triple-negative breast cancer (TNBC), are not well studied. This study aimed to identify genes related to the TME and prognosis of TNBC. Firstly, we identified differentially expressed genes (DEG) in the TME of TNBC, using Expression data (ESTIMATE) datasets obtained from the Cancer Genome Atlas (TCGA) and Estimation of Stromal and Immune cells in Malignant Tumor tissues. Next, survival analysis was performed to analyze the relationship between TME and prognosis of TNBC, as well as determine DEGs. Genes showing significant differences were scored as alternative genes. A protein-protein interaction (PPI) network was constructed and functional enrichment analysis conducted using the DEG. Proteins with a degree greater than 5 and 10 in the PPI network correspond with hub genes and key genes, respectively. Finally, CCR2 and CCR5 were identified as key genes in TME and prognosis of TNBC. Finally, these results were verified using Gene Expression Omnibus (GEO) datasets and immunohistochemistry of TNBC patients. In conclusion, CCR2 and CCR5 are key genes in the TME and prognosis of TNBC with the potential of prognostic biomarkers in TNBC.
尽管肿瘤微环境(TME)在许多癌症的发展中起着重要作用,但其在乳腺癌尤其是三阴性乳腺癌(TNBC)中的作用尚未得到充分研究。本研究旨在鉴定与TNBC的TME和预后相关的基因。首先,我们利用从癌症基因组图谱(TCGA)获得的表达数据(ESTIMATE)数据集以及恶性肿瘤组织中基质和免疫细胞的估计,鉴定TNBC的TME中差异表达基因(DEG)。接下来,进行生存分析以分析TME与TNBC预后之间的关系,并确定DEG。显示出显著差异的基因被标记为替代基因。构建了蛋白质-蛋白质相互作用(PPI)网络,并使用DEG进行了功能富集分析。在PPI网络中度数大于5和10的蛋白质分别对应于枢纽基因和关键基因。最后,CCR2和CCR5被鉴定为TNBC的TME和预后中的关键基因。最后,使用基因表达综合数据库(GEO)数据集和TNBC患者的免疫组织化学对这些结果进行了验证。总之,CCR2和CCR5是TNBC的TME和预后中的关键基因,具有作为TNBC预后生物标志物的潜力。