Role and molecular mechanisms of HuangQiSiJunZi decoction for treating triple-negative breast cancer as explored via network pharmacology and bioinformatics analyses.

Objective: In this study, we evaluated the molecular mechanisms of HuangQiSiJunZi Decoction (HQSJZD) for treating triple-negative breast cancer (TNBC) using network pharmacology and bioinformatics analyses.

Methods: Effective chemical components together with action targets of HQSJZD were selected based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Meanwhile, differentially expressed genes (DEGs) were extracted from TNBC sample data in The Cancer Genome Atlas (TCGA) database. Additionally, we built a protein-protein interaction (PPI) network and acquired hub genes. Gene Expression Omnibus(GEO) datasets were utilized to verify the accuracy of hub gene expression. Additionally, enrichment analyses were conducted on key genes. Furthermore, TNBC severity-related high-risk factors were screened through univariate together with multivariate Cox regressions; next, the logistic regression prediction model was built. Moreover, differential levels of 22 immune cell types in TNBC tissues compared with normal tissues were analyzed. The hub gene levels within pan-cancer and the human body were subsequently visualized and analyzed. Finally, quantitative PCR (RT-qPCR) was used to validate the correlation of the hub genes in TNBC cells.

Results: The study predicted 256 targets of active ingredients and 1791 DEGs in TNBC, and obtained 16 hub genes against TNBC. The prognostic signature based on FOS, MMP9, and PGR was independent in predicting survival. A total of seven types of immune cells, such as CD4 + memory T cells, showed a significant difference in infiltration (p < 0.05), and immune cells were related to the hub genes. The HPA database was adopted for hub gene analyses, and as determined, FOS was highly expressed in most human organs. The results of RT-qPCR validation for the FOS hub gene were consistent with those of bioinformatic analyses.

Conclusion: HQSJZD might regulate the interleukin-17 and aging pathways via FOS genes to increase immune cell infiltration in TNBC tissues, and thus, may treat TNBC and improve the prognosis. The FOS genes are likely to be a new marker for TNBC.