Single-cell RNA sequencing and bulk sequencing reveal the immunosuppressive role of malignant cells in triple-negative breast cancer

IF 1 Q4 GENETICS & HEREDITY Gene Reports Pub Date : 2024-06-13 DOI:10.1016/j.genrep.2024.101952

Rumeng Hu , Ming Chen , Xiaowei Fan , Menglu Zhao , Xi Huang , Jun Zhang

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Abstract

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and the limiting efficacy is achieved for TNBC patients with immunotherapy. The role of malignant cells in the tumor microenvironment (TME) is still complicated. Here, we firstly identified and characterized the malignant cells in the TME of TNBC based on single-cell and bulk RNA sequencing. Then a high score of gene copy number variation (CNV) was found in the malignant cells. And 2507 up-regulated genes and 830 down-regulated genes were obtained based on a difference analysis between the malignant cells and other epithelial cells. Furthermore, KLF3-targeted genes were identified as being associated with the development of breast cancer. Finally, an immunosuppressive role of the malignant cells was identified in the TME of TNBC as the strong interactions between tumor cells and CD8-positive exhausted T cells. Together, these findings provide new insights into the malignant cells of TME and a new idea to develop therapeutic strategy for immunotherapy of TNBC.

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单细胞 RNA 测序和批量测序揭示了三阴性乳腺癌中恶性细胞的免疫抑制作用

三阴性乳腺癌（TNBC）是侵袭性最强的乳腺癌亚型，免疫疗法对TNBC患者的疗效有限。恶性细胞在肿瘤微环境（TME）中的作用仍很复杂。在这里，我们首先基于单细胞和大体RNA测序鉴定了TNBC肿瘤微环境中的恶性细胞并对其进行了定性。然后在恶性细胞中发现了高分辨率的基因拷贝数变异（CNV）。根据恶性细胞与其他上皮细胞的差异分析，得出了2507个上调基因和830个下调基因。此外，还发现 KLF3 靶向基因与乳腺癌的发生有关。最后，由于肿瘤细胞与 CD8 阳性衰竭 T 细胞之间的强烈相互作用，在 TNBC 的 TME 中发现了恶性细胞的免疫抑制作用。总之，这些发现提供了对TME恶性细胞的新认识，并为开发TNBC免疫疗法的治疗策略提供了新思路。

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来源期刊

Gene Reports Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.30

自引率

7.70%

发文量

246

审稿时长

49 days

期刊介绍： Gene Reports publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses. Gene Reports strives to be a very diverse journal and topics in all fields will be considered for publication. Although not limited to the following, some general topics include: DNA Organization, Replication & Evolution -Focus on genomic DNA (chromosomal organization, comparative genomics, DNA replication, DNA repair, mobile DNA, mitochondrial DNA, chloroplast DNA). Expression & Function - Focus on functional RNAs (microRNAs, tRNAs, rRNAs, mRNA splicing, alternative polyadenylation) Regulation - Focus on processes that mediate gene-read out (epigenetics, chromatin, histone code, transcription, translation, protein degradation). Cell Signaling - Focus on mechanisms that control information flow into the nucleus to control gene expression (kinase and phosphatase pathways controlled by extra-cellular ligands, Wnt, Notch, TGFbeta/BMPs, FGFs, IGFs etc.) Profiling of gene expression and genetic variation - Focus on high throughput approaches (e.g., DeepSeq, ChIP-Seq, Affymetrix microarrays, proteomics) that define gene regulatory circuitry, molecular pathways and protein/protein networks. Genetics - Focus on development in model organisms (e.g., mouse, frog, fruit fly, worm), human genetic variation, population genetics, as well as agricultural and veterinary genetics. Molecular Pathology & Regenerative Medicine - Focus on the deregulation of molecular processes in human diseases and mechanisms supporting regeneration of tissues through pluripotent or multipotent stem cells.