Liver cancer is an extraordinarily heterogeneous malignant disease. The tumor microenvironment (TME) and tumor-associated macrophages (TAMs) are the major drivers of
liver cancer initiation and progression. It is critical to have a better understanding of the complicated interactions between
liver cancer and the immune system for the development of
cancer immunotherapy. Based on the gene expression profiles of
tumor immune infiltration cells (TIICs), upregulated genes in TAMs and downregulated genes in other types of immune cells were identified as macrophage-specific genes (
MSG). In this study, we combined
MSG, immune subtypes, and clinical information on
liver cancer to develop a
tumor immune infiltration macrophage signature (TIMSig). A four-gene signature (S100A9, SLC22A15, TRIM54, and PPARGC1A) was identified as the TAM-related prognostic genes for
liver cancer, independent of multiple clinicopathological parameters. Survival analyses showed that patients with low TIMSig had a superior survival rate than those with high TIMSig. Additionally, clinical
immunotherapy response and TIMSig was observed as highly relevant. In addition, TIMSig could predict the response to
chemotherapy. Collectively, the TIMSig could be a potential tool for risk-stratification, clinical decision making, treatment planning, and oncology immunotherapeutic drug development.