Construction of a tumor immune infiltration macrophage signature for predicting prognosis and immunotherapy response in liver cancer

Anmin Huang; Bei Lv; Yunjie Zhang; Junhui Yang; Jie Li; Chengjun Li; Zhijie Yu; Jinglin Xia

doi:10.3389/fmolb.2022.983840

Construction of a tumor immune infiltration macrophage signature for predicting prognosis and immunotherapy response in liver cancer

Front Mol Biosci. 2022 Sep 2:9:983840. doi: 10.3389/fmolb.2022.983840. eCollection 2022.

Authors

Anmin Huang^{1

2

3}, Bei Lv⁴, Yunjie Zhang^{1

2

3}, Junhui Yang^{1

2

3}, Jie Li^{1

2

3}, Chengjun Li^{1

2

3}, Zhijie Yu⁵, Jinglin Xia^{1

6

7}

Affiliations

¹ Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Translational Medicine Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
³ The First Clinical Medical College, Wenzhou Medical University, Wenzhou, China.
⁴ Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
⁵ Wenzhou Key Laboratory of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁶ Department of Intervention, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁷ Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Abstract

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.

Keywords: immune infiltration; immunotherapy response; macrophage; prognosis; tumor microenvironment.