Loss of Monocyte in Tumor Microenvironment Promotes Metastasis Based on Large-Scale Prostate Cancer Cohorts

Abstract

To analyze the differences and distinct features of immune cell infiltration between metastasis and primary prostate cancer. We merged multiple datasets and collected a total of 2115 prostate samples. Using single-sample Gene Sets Enrichment Analysis to calculate the abundance fraction of immune cell infiltration. Weighted-gene correlation network analysis was applied to identify gene modules related to immune infiltration. Single-cell sequencing analysis and invasion assays were used to validate the effects of immune cell on prostate cancer. In metastatic prostate cancer, the immune score was lower compared with primary and benign samples. Concretely, 16 different immune cell types especially mast cell and monocyte presented decreased abundance in the metastatic microenvironment. Furthermore, the loss of monocyte facilitating prostate cancer metastatic progression was validated by trajectory analysis and invasion assays in vitro. We found that loss of immune infiltration was a distinct characteristic of immune infiltration in the metastatic prostate cancer microenvironment. Funding Statement: This work was supported by the National Natural Science Foundation of China [81672546, 81602253, 81772703, 81872083], Natural Science Foundation of Beijing Municipality [7152146, 7172219]. Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: The study was approved by the institutional ethics committees of Peking University First Hospital. All procedures in this study were conducted in accordance with ethical principles.