Previous studies have developed a number of tumour molecular signatures for breast cancer.[6] The assessment of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 is mandatory for all invasive breast tumors, and have been widely used in clinical practice.[6] But outcomes of studying patients based on a single gene lack of accuracy. Lack of effective and reliable prognostic biomarkers still remains a major problem to improve the clinical outcomes of breast cancer patients. The relationship between lipid metabolism and cancer is multifaceted. Recent studies have shown that reprogramming of cellular lipid metabolism directly leads to malignant transformation and progression.[8, 9] It broadened our understanding of how lipid metabolism was relevant to cancer biology. To our knowledge, this study is the first to use LMGs to predict the prognosis of BC. In this study, we comprehensively analyzed 193 LMGs in BC samples and their relationships with prognosis. In functional analyses, these genes were significantly enriched in several immune cell types and immune-related pathways.
We identified 116 DEGs that were significantly differentially expressed between BC samples
and adjacent non-cancer samples, supporting the general importance of lipid metabolism in the pathogenesis and progression of BC. Moreover, we found 18 of these genes were related to OS in a univariate Cox regression analysis. These results demonstrated the importance of studying LMGs in breast tumors. The combination of univariate analysis and LASSO Cox regression was conducted to screen genes to indicate either poor or good prognosis and to construct a robust gene signature, which has been used widely in studies.[10–12] In the result, we established a new lipid-related 16-gene signature. According to the results of the ROC curve, the AUC of the risk score established by 16 LMGs was more than 0.7. This result showed that the risk score established by these 16 LMGs had a high value for predicting prognosis.
In recent years, the tumor microenvironment (TME) has been a research hotspot. During BC progression, tumor immune microenvironment remodeling with the changing of the ratio of immune cells and releasing of multiple immune inhibitory and reactive cytokines is a critical feature.[13, 14] The role of the tumor microenvironment (TME) in breast cancer immunomodulation is vitally important,[15] a better understanding of the immune cell infiltrate in the breast cancer microenvironment is crucial for the development of more effective therapeutic approaches.[16] By analyzing the pathways and functions of genes enriched in differences between the high and low risk groups, we observed a strong association with immune function. Given the above situation, we intended to unearth more information about the immunological characteristics of the LMGs signature. As excepted, patients in the low-risk groups had higher fractions of CD8 + T cells and NK cells. CD8 + T cells are the main kind of cytolytic lymphocytes in tumors, while NK cells, a type of cytotoxic lymphocytes, are crucial constituents of the innate immune system and play a key role in immune surveillance.[15] This phenomenon may indicate that CD8 + T cells and NK cells are correlated with a favorable prognosis in tumor due to their ability to target and kill tumor cells, consistent with previous studies.[17–21] PD-1 and PD-L1 constitute an essential inhibitory mechanism which causes T cell exhaustion. That's the main reason why PD-L1 has drawn increasing attention of researchers concerned.[22–24] There have been many studies of lipid metabolism effects on tumor immunity. Recently, a potent sphingolipid metabolite regulated tumorigenesis, and responsed to chemotherapy and immunotherapy by affecting the trafficking, differentiation or effector function of tumor-infiltrating immune cells (TIICs), and implicated in many processes that are important for BC.[25] But the potential mechanism of LMGs and tumor immune microenvironment in BC prognosis remains unknown, and requires further investigation.