Identification of testicular cancer immune infiltrates and novel immune cell subtypes.

Abstract

Testicular germ cell tumors (TGCT) are the most common type of testicular cancer, comprising 90%-95% of cases and representing the most prevalent solid malignancy in young adult men. Immune infiltrates play important regulatory roles in tumors, but their role in TGCT remains unclear. Molecular subtyping is a promising way to provide precisely personalized treatment and avoid unnecessary toxicities. This study investigated immune infiltrates, key biomarkers, and immune subtyping of TGCT. In GSE3218, 24 differentially expressed immune genes (immDEGs) were identified. A new risk signature consisting of six immDEGs was developed using these genes. Individuals in the high-risk group had poor overall survival (OS) (hazard ratio of 4.61 and P-value <0.001). We validated the six-immDEGs risk signature in pure seminoma and mixed TGCT types. Two distinct immune patterns (Cluster 1 and Cluster 2) were identified using the ConsensusClusterPlus, and Cluster 1 possessed an unfavorable OS compared to Cluster 2 (hazard ratio, 2.56; P <0.001). Cluster 1 patients had significantly lower naive B cells, memory B cells, plasma cells, naive CD4 T cells, gamma delta T cells, and activated dendritic cells than Cluster 2 patients. Genes relating to the WNT signaling pathway, TGF-β signaling pathway, antigen processing and presentation, and NK cell-mediated cytotoxicity were associated with TGCT. STC1 was elevated in TGCT tissues, and its high expression showed advanced clinicopathological characteristics and poor prognosis of TGCT. Our findings may contribute to increased understanding of the onset and progression of TGCT.