Wuxi Maternal and Child Health Hospital, Wuxi Medical Center of Nanjing Medical University, 214023, Wuxi, China.
The First Clinical Medical College, Nanjing Medical University, 211166, Nanjing, China.
Br J Cancer. 2023 Nov;129(10):1645-1657. doi: 10.1038/s41416-023-02432-6. Epub 2023 Sep 15.
It has been acknowledged that the tumour immune microenvironment (TIME) plays a critical role in determining therapeutic responses and clinical outcomes in breast cancer (BrCa). Thus, the identification of the TIME features is essential for guiding therapy and prognostic assessment for BrCa.
The heterogeneous cellular composition of the TIME in BrCa by single-cell RNA sequencing (scRNA-seq). Two subtype-special genes upregulated in the tumour-rich subtype and the immune-infiltrating subtype were extracted, respectively. The CRABP2/CD69 signature was established based on CRABP2 and CD69 expression, and its predictive values for the clinical outcome and the neoadjuvant chemotherapy (NAT) responses were validated in multiple cohorts. Moreover, the oncogenic role of CRABP2 was explored in BrCa cells.
Based on the heterogeneous cellular composition of the TIME in BrCa, the BrCa samples could be divided into the tumour-rich subtype and the immune-infiltrating subtype, which exhibited distinct prognosis and chemotherapeutic responses. Next, we extracted CRABP2 as the biomarker for the tumour-rich subtype and CD69 as the biomarker for the immune-infiltrating subtype. Based on the CRABP2/CD69 signature, BrCa samples were re-divided into three subtypes, and the CRABP2CD69 subtype exhibited the worst prognosis and the lowest chemotherapeutic response, while the CRABP2CD69 subtype showed the opposite results. Furthermore, CARBP2 functioned as a novel oncogene in BrCa, which promoted tumour cell proliferation, migration, and invasion, and CRABP2 inhibition triggered the activation of cytotoxic T lymphocytes (CTLs).
The CRABP2/CD69 signature is significantly associated with the TIME features and could effectively predict the clinical outcome. Also, CRABP2 is determined to be a novel oncogene, which could be a therapeutic target in BrCa.
肿瘤免疫微环境（TIME）在确定乳腺癌（BrCa）的治疗反应和临床结局方面起着关键作用。因此，识别 TIME 特征对于指导 BrCa 的治疗和预后评估至关重要。
通过单细胞 RNA 测序（scRNA-seq）分析 BrCa 中 TIME 的异质性细胞组成。分别提取在肿瘤丰富亚型和免疫浸润亚型中上调的两个亚型特异性基因。基于 CRABP2 和 CD69 的表达建立 CRABP2/CD69 特征，并在多个队列中验证其对临床结局和新辅助化疗（NAT）反应的预测价值。此外，还在 BrCa 细胞中探索了 CRABP2 的致癌作用。
基于 BrCa 中 TIME 的异质性细胞组成，可将 BrCa 样本分为肿瘤丰富亚型和免疫浸润亚型，它们表现出不同的预后和化疗反应。接下来，我们提取 CRABP2 作为肿瘤丰富亚型的生物标志物，CD69 作为免疫浸润亚型的生物标志物。基于 CRABP2/CD69 特征，可将 BrCa 样本重新分为三个亚型，其中 CRABP2CD69 亚型表现出最差的预后和最低的化疗反应，而 CRABP2CD69 亚型则表现出相反的结果。此外，CARBP2 在 BrCa 中作为一种新的癌基因发挥作用，它促进肿瘤细胞的增殖、迁移和侵袭，而 CRABP2 抑制则触发细胞毒性 T 淋巴细胞（CTLs）的激活。
CRABP2/CD69 特征与 TIME 特征显著相关，可有效预测临床结局。此外，CRABP2 被确定为一种新的癌基因，可作为 BrCa 的治疗靶点。
