Zhang Bi-Tian, Song Xiaoyu, Cho Chi-Shing William, Wong Chun-Kwok, Wang Dongjie
Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants, The Chinese University of Hong Kong, Hong Kong, China.
School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China.
Cancers (Basel). 2025 Apr 26;17(9):1455. doi: 10.3390/cancers17091455.
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related mortality, particularly in advanced stages. This study investigates the anticancer mechanisms of calycosin, an isoflavonoid derived from , in LUAD.
Using integrative approaches including bulk and single-cell RNA sequencing, network pharmacology, and molecular docking, we identified SMAD3 as a critical biomarker associated with LUAD staging and prognosis.
Calycosin targets SMAD3, modulating the NOTCH signaling pathway in monocytes/macrophages to suppress tumor growth, invasion, and immune evasion. Enrichment analyses revealed significant involvement of NOTCH signaling components in SMAD3-correlated genes, particularly in advanced-stage LUAD. Single-cell RNA sequencing further demonstrated NOTCH pathway enrichment in tumor-associated monocytes/macrophages. Additionally, KMT2A was identified as a key transcriptional regulator in these cells.
These findings highlight the potential effects of calycosin and provide novel insights into targeting the tumor-immune microenvironment in LUAD.
肺腺癌（LUAD）仍然是癌症相关死亡的主要原因，尤其是在晚期。本研究调查了毛蕊异黄酮（一种从[来源未提及]衍生的异黄酮）在LUAD中的抗癌机制。
我们采用包括批量和单细胞RNA测序、网络药理学和分子对接在内的综合方法，确定SMAD3是与LUAD分期和预后相关的关键生物标志物。
毛蕊异黄酮靶向SMAD3，调节单核细胞/巨噬细胞中的NOTCH信号通路，以抑制肿瘤生长、侵袭和免疫逃逸。富集分析显示NOTCH信号成分在与SMAD3相关的基因中显著参与，特别是在晚期LUAD中。单细胞RNA测序进一步证明了肿瘤相关单核细胞/巨噬细胞中NOTCH通路的富集。此外，KMT2A被确定为这些细胞中的关键转录调节因子。
这些发现突出了毛蕊异黄酮的潜在作用，并为靶向LUAD中的肿瘤免疫微环境提供了新的见解。
