Wang Huiling, Dai Huijuan, Zhou Liheng, Lin Yanping, Yin Wenjin, Lu Jingsong
Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Oncol. 2025 Jul 29;15:1587236. doi: 10.3389/fonc.2025.1587236. eCollection 2025.
Triple-negative breast cancer (TNBC) represents the most aggressive breast cancer subtype. The limited treatment options underscore the urgent need to explore novel molecular targets to combat TNBC progression. This study investigates the oncogenic functions of SHCBP1 in TNBC.
Bulk RNA-seq and single-cell sequencing (scRNA-seq) data for TNBC samples were acquired from the Cancer Genome Atlas (TCGA) dataset and GSE161529, respectively. SHCBP1 expression at the mRNA and protein levels was compared between TNBC and normal breast tissues. The prognostic significance of SHCBP1 in TNBC was assessed using Kaplan-Meier analysis. The potential biological functions of SHCBP1 were explored through gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Immunofluorescence was utilized to determine the subcellular localization of SHCBP1 during cell division. Quantitative PCR (qPCR) and western blotting were employed to measure SHCBP1 expression in breast cancer cell lines. Subsequently, the impact of SHCBP1 on TNBC cell proliferation and migration was evaluated . Finally, scRNA-seq analysis was conducted to characterize SHCBP1 expression patterns at the single-cell resolution.
SHCBP1 is markedly upregulated in TNBC tissues, and its overexpression is associated with poorer survival outcomes. Functional enrichment analysis reveals that SHCBP1-related genes are significantly enriched in pathways involved in cell-cycle regulation and DNA damage response. studies demonstrate that SHCBP1 enhances TNBC cell proliferation and migration. The scRNA-seq analysis displays the cell clusters in which SHCBP1 is primarily expressed. Cancer epithelial cells exhibiting higher SHCBP1 expression display stronger interactions with stromal cells in the tumor microenvironment.
This study elucidates the critical role of SHCBP1 in TNBC progression, highlighting its potential as a therapeutic target. These findings provide a foundation for further exploration of SHCBP1 in TNBC treatment strategies.
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型。治疗选择有限凸显了探索新的分子靶点以对抗TNBC进展的迫切需求。本研究调查了SHCBP1在TNBC中的致癌功能。
分别从癌症基因组图谱（TCGA）数据集和GSE161529获取TNBC样本的批量RNA测序和单细胞测序（scRNA-seq）数据。比较TNBC和正常乳腺组织中SHCBP1在mRNA和蛋白质水平的表达。使用Kaplan-Meier分析评估SHCBP1在TNBC中的预后意义。通过基因本体（GO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）探索SHCBP1的潜在生物学功能。利用免疫荧光确定细胞分裂过程中SHCBP1的亚细胞定位。采用定量PCR（qPCR）和蛋白质印迹法测量乳腺癌细胞系中SHCBP1的表达。随后，评估SHCBP1对TNBC细胞增殖和迁移的影响。最后，进行scRNA-seq分析以在单细胞分辨率下表征SHCBP1的表达模式。
SHCBP1在TNBC组织中显著上调，其过表达与较差的生存结果相关。功能富集分析表明，与SHCBP1相关的基因在参与细胞周期调控和DNA损伤反应的途径中显著富集。研究表明，SHCBP1增强TNBC细胞的增殖和迁移。scRNA-seq分析显示了SHCBP1主要表达的细胞簇。SHCBP1表达较高的癌症上皮细胞在肿瘤微环境中与基质细胞表现出更强的相互作用。
本研究阐明了SHCBP1在TNBC进展中的关键作用，突出了其作为治疗靶点的潜力。这些发现为进一步探索SHCBP1在TNBC治疗策略中的应用奠定了基础。
