SPP1 mRNA Expression Is Associated with M2 Macrophage Infiltration and Poor Prognosis in Triple-Negative Breast Cancer

(1): Triple-negative breast cancer (TNBC) is an especially aggressive form of breast cancer defined by a poor prognosis and a lack of effective treatment options. There is a pressing need for validated predictive and prognostic biomarkers to assist in making treatment decisions and improve the prognostic accuracy for patients with this challenging disease. (2): We analyzed the RNA-seq data from three TNBC tissue samples alongside their corresponding normal tissues. Gene set enrichment analysis (GSEA) identified potential pathways. Additionally, we examined SPP1 mRNA expression datasets available in the Kaplan-Meier plotter and investigated the SPP1 protein expression patterns in our own tissue microarray cohort via immunohistochemistry. (3): The results revealed that genes associated with the Toll-like receptor signaling pathway showed a significant increase in activity in TNBC tissues when compared to normal breast tissues. Furthermore, SPP1 expression was found to be elevated in the TCGA TNBC dataset and correlated with a poor prognosis. This pattern was corroborated at the protein level in our TNBC tissue cohort; however, SPP1 protein expression did not demonstrate a significant impact on survival. Notably, SPP1 mRNA expression was strongly linked to tumor-associated macrophages (TAMs), particularly the M2 macrophage subtype, indicating a substantial association in the context of TNBC. (4): Our research highlights the significance of SPP1 mRNA as a key prognostic indicator and a potential molecular responder for TNBC treatment utilizing targeted therapies that focus on Toll-like receptor signaling pathways.