Department of Mathematics, Yunnan Normal University, Kunming 650500, China.
Key Laboratory Complex System Modeling and Application for Universities in Yunnan, Kunming 650500, China.
Int J Mol Sci. 2023 Feb 17;24(4):4058. doi: 10.3390/ijms24044058.
Dendritic cells(DCs) play a protective role in the antitumor immunity of most cancers, which can be divided into conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs). Most current studies are only based on either cDCs or pDCs for the study of the relationship between DCs and breast cancer prognosis, without combining the two together. We aimed to select new biomarkers from pDCs and cDCs. In this paper, the xCell algorithm was first used to calculate the cellular abundance of 64 types of immune cells and stromal cells in tumor samples from the TCGA database, and the high-abundance pDC group and cDC group were divided according to the results of a survival analysis. Then, we looked for the co-expressed gene module of highly infiltrating pDC and cDC patients with a weighted correlation network analysis (WGCNA) and screened out the hub genes, including , , , , and . Finally, we analyzed the biological functions of the hub genes, and the results showed that , , and were significantly related to the immune cells and prognosis of patients, and and were involved in responding to TCF-related instructions of the Wnt pathway. In addition, we also evaluated the response of pDCs and cDCs with different abundances to chemotherapy, and the results showed that the higher the abundance of pDCs and cDCs, the higher their sensitivity to drugs. This paper revealed new biomarkers related to DCs-among them, , , and were proven to be closely related to dendritic cells in cancer. For the first time, this paper puts forward that and are related to the prognosis of dendritic cells in cancer, which also provides new possibilities for finding new targets for breast cancer immunotherapy.
树突状细胞（DCs）在大多数癌症的抗肿瘤免疫中发挥保护作用，可分为经典树突状细胞（cDCs）和浆细胞样树突状细胞（pDCs）。目前大多数研究仅基于 cDCs 或 pDCs 来研究 DCs 与乳腺癌预后的关系，而没有将两者结合起来。我们旨在从 pDCs 和 cDCs 中选择新的生物标志物。在本文中，首先使用 xCell 算法计算 TCGA 数据库中肿瘤样本中 64 种免疫细胞和基质细胞的细胞丰度，并根据生存分析的结果将高丰度的 pDC 组和 cDC 组进行分组。然后，我们使用加权相关网络分析（WGCNA）寻找高浸润性 pDC 和 cDC 患者的共表达基因模块，并筛选出枢纽基因，包括、、、、和。最后，我们分析了枢纽基因的生物学功能，结果表明、、和与患者的免疫细胞和预后显著相关，和参与了 Wnt 通路中 TCF 相关指令的反应。此外，我们还评估了具有不同丰度的 pDCs 和 cDCs 对化疗的反应，结果表明 pDCs 和 cDCs 的丰度越高，对药物的敏感性越高。本文揭示了与 DCs 相关的新生物标志物，其中、、和被证明与癌症中的树突状细胞密切相关。本文首次提出和与癌症中树突状细胞的预后相关，这也为寻找乳腺癌免疫治疗的新靶点提供了新的可能性。
