Abstract
Runt-related transcription factors (RUNXs) can serve as both transcription activators and repressors during biological development, including immune cell maturation. RUNX factors have both tumor-promoting and tumor-suppressive roles in carcinogenesis. Immune cell infiltration and the tumor immune microenvironment have been found to be key regulators in breast cancer progression, treatment response, and patient outcome. However, the relationship between the RUNX family and immune cell infiltration in breast cancer remains unclear. We performed a comprehensive analysis to reveal the role of RUNX factors in breast cancer. Analysis of patient data in the Oncomine database showed that the transcriptional levels of RUNX proteins in breast cancer were elevated. Kaplan–Meier plotter (KM plotter) analysis showed that breast cancer patients with higher expression of RUNX proteins had better survival outcomes. Through analysis of the UALCAN database, we found that the transcriptional levels of RUNX factors were significantly correlated with some breast cancer patient characteristics. cBio Cancer Genomics Portal (cBioPortal) analysis showed the proportions of different RUNX genomic alterations in various subclasses of breast cancer. We also performed gene ontology (GO) and pathway analyses for the significantly differentially expressed genes that were correlated with RUNX factors in breast cancer. TIMER database analysis showed that immune cell infiltration in breast cancer could be affected by the transcriptional level, mutation, and gene copy number of RUNX proteins. Using the Gene Set Cancer Analysis (GSCA) database, we analyzed the effects of RUNX gene methylation on the level of immune cell infiltration in breast cancer. We found that the methylation level changes of RUNX2 and RUNX3 had opposite effects on immune cell infiltration in breast cancer. We also analyzed the relationship between the methylation level of RUNX genes and the TGF-β signaling pathway using the TISIDB database. The results showed that the methylation levels of RUNX1 and RUNX3 were correlated with the expression of TGF-β1. In summary, our analysis found that the RUNX family members can influence the infiltration of various immune cells in breast cancer depending on their expression level, mutation, gene copy number, and methylation. The RUNX family is an important regulator of immune cell infiltration in breast cancer and may serve as a potential prognostic biomarker.
Highlights
Breast cancer is the most common cancer type among women and is one of the leading causes of cancer-related deaths worldwide (Siegel et al, 2021)
We found that the expression level of RUNX1 was significantly associated with the stage of breast cancer (p = 0.0001), while there was no significant difference in RUNX2 and RUNX3 expression (Figure 2)
We found that RUNX2 expression significantly varied in different stages, subclasses, and histological subtypes of breast cancer (Supplementary Figure 1)
Summary
Breast cancer is the most common cancer type among women and is one of the leading causes of cancer-related deaths worldwide (Siegel et al, 2021). With improvements in diagnostic techniques and precise treatments, the overall prognosis of breast cancer patients has substantially improved in recent years. Not all patients respond favorably to current therapy, and relapse is common. This is due to the complex nature of breast cancer pathogenesis, development, and metastasis. The role of tumor-infiltrating immune cells in breast cancers and their effects on tumor progression and immunotherapy are gaining attention (Azizi et al, 2018). Clinical data-based analysis has indicated a significant impact of tumorinfiltrating immune cells on the clinical outcome of breast cancer patients, including treatment response, recurrence, and death (Adams et al, 2014; Ali et al, 2014; Loi et al, 2014). It is necessary to characterize the immune microenvironment of breast cancer, develop biomarkers to facilitate precise patient stratification, and provide potential therapeutic molecular targets to modulate the breast cancer microenvironment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
