基于单细胞和空间转录组的苦参碱在宫颈癌中的代谢-免疫相互作用网络及治疗靶点发现

Although its exact mechanism is yet unknown, cervical cancer is a very common malignant tumor in the world. Its growth is strongly linked to metabolic imbalance and tumor microenvironment heterogeneity.

Further research is necessary to determine if the natural substance matrine's multi-targeted anti-tumor capability is due to metabolic reprogramming or immune microenvironment regulation. The purpose of this study is to provide a new research direction and theoretical foundation for the treatment of cervical cancer by thoroughly examining the molecular mechanism of the disease and assessing the potential of matrine intervention through the integration of TCGA database analysis, single-cell sequencing, and spatial transcriptome technology.

To extensively examine the differential gene expression characteristics, immune microenvironment heterogeneity, and metabolic pathway regulation network of cervical cancer, we combined TCGA database analysis, single-cell sequencing, and spatial transcriptome technologies. The immune and stromal scores of tumor tissues were evaluated using the CIBERSORT and ESTIMATE algorithms, and the metabolic-immune interactions between immune and malignant cells were discovered by single-cell sequencing.

Furthermore, matrine's mode of action was examined using bioinformatics, and its possible therapeutic targets were preliminarily indicated using in vitro tests and molecular docking. Using TCGA database analysis, 758 differential genes were screened for this investigation. Of these, 453 overlapped with cervical cancer targets in the CTD database.

Additionally, 20 hub genes were found, primarily involved in DNA damage repair, chromosome segregation, and cell cycle regulation. Enrichment study revealed that cervical cancer has markedly activated metabolic pathways, including the calcium signaling pathway, the neuroactive ligand-receptor interaction, and glycolysis/tricarboxylic acid cycle (TCA). While CD8 + T cell function may be inhibited, immuno-microenvironmental examination showed a considerable increase in the infiltration of neutrophils, NK cells, and macrophages in tumor tissues.

Furthermore, by targeting genes that control calcium signaling, cAMP, and inflammation-related pathways, including BCHE, HTR2B, PLA2G2C, PTGER3, and TACR1, this intervention may have the potential to suppress tumor malignancy. By combining multilevel data, this study uncovers the fundamental mechanism of the metabolism-immunity interaction in cervical cancer and suggests a novel approach for hormone-targeted therapy.

Our preliminary results indicate that this treatment can upregulate or downregulate certain genes associated with malignant tumors at the mRNA level.