Integrative Analysis of Bulk RNA-Seq and Single-Cell RNA-Seq Unveils the Characteristics of the Immune Microenvironment and Prognosis Signature in Prostate Cancer.

ABSTRACT

The immune microenvironment is a culmination of the collaborative effort of immune cells and is important in cancer development. The underlying mechanisms of the tumor immune microenvironment in regulating prostate cancer (PRAD) are unclear. In the current study, 144 natural killer cell-related genes were identified using differential expression, single-sample gene set enrichment analysis, and weighted gene coexpression network analysis. Furthermore, VCL, ACTA2, MYL9, MYLK, MYH11, TPM1, ACTG2, TAGLN, and FLNC were selected as hub genes via the protein-protein interaction network. Based on the expression patterns of the hub genes, endothelial, epithelial, and tissue stem cells were identified as key cell subpopulations, which could regulate PRAD via immune response, extracellular signaling, and protein formation. Moreover, 27 genes were identified as prognostic signatures and used to construct the risk score model. Receiver operating characteristic curves revealed the good performance of the risk score model in both the training and testing datasets. Different chemotherapeutic responses were observed between the low- and high-risk groups. Additionally, a nomogram based on the risk score and other clinical features was established to predict the 1-, 3-, and 5-year progression-free interval of patients with PRAD. This study provides novel insights into the molecular mechanisms of the immune microenvironment and its role in the pathogenesis of PARD. The identification of key cell subpopulations has a potential therapeutic and prognostic use in PRAD.