Expression of squalene epoxidase and PRDM16 is high in breast cancer with adipose stroma

Introduction Adipose tissue constitutes a significant portion of the breast tumor microenvironment (TME), influencing lipid metabolism and cancer progression. Squalene epoxidase (SQLE), a key enzyme in cholesterol biosynthesis, and PRDM16, involved in adipogenesis and metabolic regulation, have been implicated in tumor biology. However, the impact of stromal composition on SQLE and PRDM16 expression in breast cancer remains unclear. Methods We analyzed the expression of SQLE and PRDM16 in breast cancer samples categorized into adipose-rich and fibrous stromal subtypes. Immunohistochemistry (IHC) was performed on tissue microarrays, and co-culture experiments with 3T3-L1 and NIH-3T3 cells were conducted using breast cancer cell lines representing different molecular subtypes. Protein and mRNA levels of SQLE and PRDM16 were assessed using Western blotting and quantitative real-time PCR. The prognostic significance of SQLE and PRDM16 expression was evaluated through survival analysis. Results SQLE and PRDM16 expression were significantly higher in breast cancers with adipose stroma than those with fibrous stroma (p < 0.001 and p = 0.007, respectively). Co-culture with 3T3-L1 induced SQLE and PRDM16 expression in HER2-overexpressing and triple-negative breast cancer (TNBC) cell lines but had minimal effects on Luminal and HER2-positive subtypes. In contrast, NIH-3T3 co-culture did not significantly alter their expression. Survival analysis indicated that PRDM16 expression was associated with shorter overall survival (p = 0.049), while SQLE expression did not considerably impact prognosis. Conclusion Our findings suggest that adipose stroma promotes SQLE and PRDM16 expression, particularly in aggressive breast cancer subtypes. PRDM16 may be a potential prognostic marker, influencing tumor progression through metabolic and stromal interactions. Further studies are needed to elucidate the mechanistic role of PRDM16 and SQLE in the breast cancer microenvironment.