Wang Guixin, Shi Cangchang, He Long, Li Yingxi, Song Wenbin, Chen Zhaohui, Liu Zhaoyi, Wang Yizeng, He Xianghui, Yu Yue, Tian Yao, Wang Xin
the First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huan-Hu-Xi Road, He-Xi District, Tianjin, 300060, China.
Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.
Cancer Cell Int. 2024 Sep 18;24(1):319. doi: 10.1186/s12935-024-03505-z.
Tumor metastasis is a continuous and dynamic process and is a major cause of tumor-related death in triple-negative breast cancer. However, this biological process remains largely unknown in triple-negative breast cancer. The emergence of single-cell sequencing enables a deeper understanding of the tumor microenvironment and provides a new strategy for discovering the potential mechanism of tumor metastasis. Herein, we integrated the single-cell expression profiling of primary and metastatic triple-negative breast cancer by Seurat package. Nine tumor cell subgroups were identified. Enrichment analysis suggested tumor subgroups (C0, C4) were associated with tumor metastasis with poor prognosis in TNBC. Weighted gene co-expression network was constructed and identified NENF was a metastasis-related gene. Subsequently, RT-qPCR, Immunohistochemistry, and western blot confirmed NENF is highly expressed in TNBC tissues. And cell function assays indicated NENF promote cell invasion and migration through regulating EMT in TNBC. Finally, TIDE and Connectivity Map database suggest the candidate drugs for targeting NENF. In conclusion, our findings provide a new insight into the progression and metastasis of TNBC and uncover NENF may be a prognostic biomarker and potential therapy targets.
肿瘤转移是一个持续且动态的过程,是三阴性乳腺癌中肿瘤相关死亡的主要原因。然而,这一生物学过程在三阴性乳腺癌中在很大程度上仍不清楚。单细胞测序的出现能够更深入地了解肿瘤微环境,并为发现肿瘤转移的潜在机制提供了新策略。在此,我们通过Seurat软件包整合了原发性和转移性三阴性乳腺癌的单细胞表达谱。鉴定出九个肿瘤细胞亚群。富集分析表明肿瘤亚群(C0、C4)与三阴性乳腺癌中预后不良的肿瘤转移相关。构建了加权基因共表达网络并鉴定出NENF是一个与转移相关的基因。随后,逆转录定量聚合酶链反应、免疫组织化学和蛋白质免疫印迹证实NENF在三阴性乳腺癌组织中高表达。并且细胞功能实验表明NENF通过调节三阴性乳腺癌中的上皮-间质转化促进细胞侵袭和迁移。最后,TIDE和连通性图谱数据库提示了靶向NENF的候选药物。总之,我们的研究结果为三阴性乳腺癌的进展和转移提供了新见解,并揭示NENF可能是一个预后生物标志物和潜在的治疗靶点。