DDHD2 is involved in the malignant progression of early luminal A breast cancer by changing cell membrane proteins and immune responses functionality

Abstract Background Luminal A breast cancer has the best prognosis of all malignant breast cancer types. In clinical practice, some patients with luminal A breast cancer present with small tumors (usually <20 mm) but with lymph node metastases or even distant organ metastasis. Owing to their insensitivity to chemotherapy and the lack of conclusive clinical evidence, there is a significant gap in research on luminal A breast cancer with high invasiveness. This study aimed to identify genes that drive the invasiveness of luminal A breast cancer and explore the underlying mechanisms. Methods In this study, we first utilized bioinformatics techniques to analyze differentially expressed mRNAs and enrich common functional pathways to identify the target gene DDHD domain containing 2 (DDHD2). We then evaluated the association between DDHD2 expression and patient prognosis, genetic material changes, and transcriptional, translational, and immune responses in luminal A breast cancer. We also conducted experiments at the molecular and cellular levels to validate these biochemical mechanisms. Results The expression of DDHD2 varied between patients with low-grade luminal A breast cancer with and without lymph node metastases. Our findings demonstrated that DDHD2 exerted carcinogenic effects through various pathways by altering cell adhesion and migration, regulating cell proliferation and apoptosis cycles, and suppressing immune responses. Moreover, a pathway through which DDHD2 inhibited immunity was preliminarily verified. Conclusions The results revealed a novel role for DDHD2 in promoting the malignant transformation and invasiveness of luminal A breast cancer. Considering its effects on the tumor microenvironment and tumor-infiltrating immune cells in the epithelial-mesenchymal transition, DDHD2 is proposed as a reliable direction for future immunotherapy and a potential target in luminal A breast cancer immune resistance.