NR2F1, a Tumor Dormancy Marker, Is Expressed Predominantly in Cancer-Associated Fibroblasts and Is Associated with Suppressed Breast Cancer Cell Proliferation

Cancers

Li Yan¹  Mariko Asaoka²  Takashi Ishikawa²  Masanori Oshi³  Arya Mariam Roy⁴  Shipra Gandhi⁴  Yoshihisa Tokumaru⁵  Rongrong Wu⁶  Kazuaki Takabe⁶ 

[1] Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo 160-8402, Japan;Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan;Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu 501-1193, Japan;Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;

关键词: breast cancer;    cancer associated fibroblasts;    dormancy;    NR2F1;    single cell sequence;    TGF beta;   

DOI  :  10.3390/cancers14122962

来源: DOAJ

【 摘 要 】

Background: Tumor dormancy is a crucial mechanism responsible for the late recurrence of breast cancer. Thus, we investigated the clinical relevance of the expression of NR2F1, a known dormancy biomarker. Methods: A total of 6758 transcriptomes of bulk tumors from multiple breast cancer patient cohorts and two single-cell sequence cohorts were analyzed. Results: Breast cancer (BC) with high NR2F1 expression enriched TGFβ signaling, multiple metastases, and stem cell-related pathways. Cell proliferation-related gene sets were suppressed, and MKi67 expression was lower in high NR2F1 BC. In tumors with high Nottingham grade, NR2F1 expression was found to be lower. There was no consistent relationship between NR2F1 expression and metastasis or survival. Cancer mutation rates, immune responses, and immune cell infiltrations were lower in high NR2F1 tumors, whereas the infiltration of stromal cells including cancer-associated fibroblasts (CAFs) was higher. NR2F1 was predominantly expressed in CAFs, particularly inflammatory CAFs, rather than in cancer cells, consistently in the two single-cell sequence cohorts. Conclusions: NR2F1 expression in breast cancer is associated with tumor dormancy traits, and it is predominantly expressed in CAFs in the tumor microenvironment.

【 授权许可】

Unknown