Integrative analysis of bulk and single-cell transcriptomics identifies factors related to immunosuppressive microenvironment to predict unfavorable prognosis in inflammatory breast cancer

Introduction Inflammatory breast cancer (IBC) is a rare invasive tumor and characterized by the formation of tumor emboli within dermal lymphatic vessels. The tumor microenvironment (TME) is a key factor in IBC aggressiveness, but its heterogeneity and intercellular role remain incompletely understood. Methods Weighted gene coexpression network analysis (WGCNA) was performed to identify immune infiltration-associated genes. We also depicted cellular communication networks and specific ligand-receptor signaling pathways using the single-cell transcriptomics analysis of IBC and non-IBC samples. Finally, we verified the expression of key proteins by immunohistochemistry. Results Through the intersection of WGCNA module genes and differentially expressed genes between pathological complete response and residual disease samples, GZMB was identified as hub gene which is related to immune infiltration and efficacy of neoadjuvant therapy in IBC. In IBC cohort, patients with high expression of GZMB harbored more immunosuppressive cells thus showed unfavorable prognosis compared with GZMB -low expression group (p