Exploring the key genes associated with breast cancer radiotherapy sensitivity based on the stromal-immune score and analysis of the WGCNA and ceRNA network

Abstract Background: Breast cancer is a highly malignant disease worldwide. Among the numerous treatment options for breast cancer, radiotherapy is one of the commonly used treatments, while there is currently no sufficient molecular biomarkers to predict prognosis and guide its application. The tumor microenvironment (TME) is an important factor affecting tumor biological function, and changes in its composition are equally relevant to tumor progression and prognosis during radiotherapy. Methods: Here, we performed bioinformatic analyses using data obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases to screen for molecular biomarkers related to TME that may influence radiotherapy sensitivity. By combining immune scores and stromal scores calculated as well as performing weighted co-expression network analysis (WGCNA), we identified key modules and hub genes to construct competing endogenous RNA (ceRNA) networks. Then, key pathways and genes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: Genes of the PI3K-AKT pathway in the blue module were significantly enriched. Among hub genes in the blue module, we further found that the expression levels of COL1A1, COL1A2, COL6A3, THBS2 and PDGFRB were negatively associated with radiotherapy sensitivity. Conclusion: These findings may provide new insights into the mechanisms of radiotherapy sensitivity in breast cancer patients, offering hope for the discovery of new therapeutic targets.