Abstract
The tumor immune microenvironment (TIME) consists of multiple cell types that contribute to the heterogeneity and complexity of prostate cancer (PCa). In this study, we sought to understand the gene-expression signature of patients with primary prostate tumors by investigating the co-expression profiles of patient samples and their corresponding clinical outcomes, in particular “disease-free months” and “disease reoccurrence”. We tested the hypothesis that the CXCL13-CXCR5 axis is co-expressed with factors supporting TIME and PCa progression. Gene expression counts, with clinical attributes from PCa patients, were acquired from TCGA. Profiles of PCa patients were used to identify key drivers that influence or regulate CXCL13-CXCR5 signaling. Weighted gene co-expression network analysis (WGCNA) was applied to identify co-expression patterns among CXCL13-CXCR5, associated genes, and key genetic drivers within the CXCL13-CXCR5 signaling pathway. The processing of downloaded data files began with quality checks using NOISeq, followed by WGCNA. Our results confirmed the quality of the TCGA transcriptome data, identified 12 co-expression networks, and demonstrated that CXCL13, CXCR5 and associated genes are members of signaling networks (modules) associated with G protein coupled receptor (GPCR) responsiveness, invasion/migration, immune checkpoint, and innate immunity. We also identified top canonical pathways and upstream regulators associated with CXCL13-CXCR5 expression and function.
Highlights
Characterization of the gene-expression signatures of prostate cancer (PCa) are important to predict patient outcomes
We took advantage of large-scale gene expression profiles of PCa patients provided by TCGA and comprehensive systems biology to identify drivers that significantly regulate the molecular signature of the tumor immune microenvironment (TIME)
We show that CXCR5 downstream signaling molecules and CXCL13 are members of the module associated with immune checkpoint, invasion/migration, innate immunity, and tertiary lymphoid structure formation
Summary
Characterization of the gene-expression signatures of PCa are important to predict patient outcomes. We sought to better understand the gene-expression signature of patients with prostate primary tumors by investigating the co-expression profiles of patient samples and their corresponding clinical outcomes, in particular “disease-free months” and “disease reoccurrence. We want to better understand the contribution of CXCL13, CXCR5 and immune-related genes within the identified co-expression profiles as it relates to patient outcomes. Chemokines and their receptors play an essential role in PCa metastasis. We took advantage of large-scale gene expression profiles of PCa patients provided by TCGA and comprehensive systems biology to identify drivers that significantly regulate the molecular signature of the TIME. Functional analysis identified key canonical pathways and upstream regulators targeting the expression of genes in this module, which included CXCL13 and CXCR5
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