Department of Breast Surgery, The First Hospital of China Medical University, Shenyang, 110001 Liaoning Province, China.
Department of Cardiovascular Ultrasound, The First Hospital of China Medical University, Shenyang, 110001 Liaoning Province, China.
Biomed Res Int. 2020 Jul 11;2020:7575862. doi: 10.1155/2020/7575862. eCollection 2020.
Cancer stem cells (CSCs) are subsets of cells with the ability of self-renewal and differentiation in neoplasm, which are considered to be related to tumor heterogeneity. It has been reported that CSCs act on tumorigenesis and tumor biology of triple-negative breast cancer (TNBC). However, the key genes that cause TNBC showing stem cell characteristics are still unclear. We combined the RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) database and mRNA expression-based stemness index (mRNAsi) to further analyze mRNAsi with regard to molecular subtypes, tumor depth, and pathological staging characteristics of breast cancer (BC). Secondly, we extract the differential gene expression of tumor vs. normal group and TNBC vs. other subtypes of BC group, respectively, and intersect them to achieve precise results. We used a weighted gene coexpression network analysis (WGCNA) to screen significant gene modules and the functions of selected genes including BIRC5, CDC25A, KIF18B, KIF2C, ORC1, RAD54L, and TPX2 were carried out through gene ontology (GO) functional annotation. The Oncomine, bc-GenExMiner v4.4, GeneMANIA, Kaplan-Meier Plotter (KM-plotter), and GEPIA were used to verify the expression level and functions of key genes. In this study, we found that TNBC had the highest stem cell characteristics in BC compared with other subtypes. The lower the mRNAsi score, the better the overall survival and treatment outcome. Seven key genes of TNBC were screened and functional annotation indicated that there were strong correlations between them, relating to nuclear division, organelle fission, mitotic nuclear division, and other events that determine cell fate. Among these genes, we found four genes that were highly associated with adverse survival events. Seven key genes identified in this study were found to be closely related to the maintenance of TNBC stemness, and the overexpression of four showed earlier recurrence. The overall survival (OS) curves of all key genes between differential expression level crossed at around nine-year follow-up, which was consistent with the trend of the OS curve related to mRNAsi. These findings may provide new ideas for screening therapeutic targets in order to depress TNBC stemness.
癌症干细胞（CSCs）是具有自我更新和分化能力的肿瘤细胞亚群，被认为与肿瘤异质性有关。已经报道 CSCs 作用于三阴性乳腺癌（TNBC）的肿瘤发生和肿瘤生物学。然而，导致 TNBC 表现出干细胞特征的关键基因仍不清楚。我们结合了来自癌症基因组图谱（TCGA）数据库的 RNA 测序（RNA-seq）数据和基于 mRNA 表达的干细胞指数（mRNAsi），进一步分析了 mRNAsi 与乳腺癌（BC）的分子亚型、肿瘤深度和病理分期特征的关系。其次，我们分别提取了肿瘤与正常组和 TNBC 与其他 BC 亚型组的差异基因表达，并将它们相交以获得精确的结果。我们使用加权基因共表达网络分析（WGCNA）筛选显著的基因模块，对 BIRC5、CDC25A、KIF18B、KIF2C、ORC1、RAD54L 和 TPX2 等选定基因的功能进行了基因本体（GO）功能注释。使用 Oncomine、bc-GenExMiner v4.4、GeneMANIA、Kaplan-Meier Plotter（KM-plotter）和 GEPIA 验证了关键基因的表达水平和功能。在这项研究中，我们发现与其他亚型相比，TNBC 在 BC 中具有最高的干细胞特征。mRNAsi 评分越低，整体生存率和治疗效果越好。筛选出 7 个 TNBC 的关键基因，功能注释表明它们之间存在很强的相关性，与核分裂、细胞器分裂、有丝分裂核分裂和其他决定细胞命运的事件有关。在这些基因中，我们发现了 4 个与不良生存事件高度相关的基因。本研究鉴定的 7 个关键基因与 TNBC 干性的维持密切相关，其中 4 个基因的高表达预示着更早的复发。所有关键基因的总生存（OS）曲线在大约 9 年的随访中在差异表达水平交叉，这与与 mRNAsi 相关的 OS 曲线的趋势一致。这些发现可能为筛选治疗靶点提供新的思路，以抑制 TNBC 的干性。
