Science and Research

Comprehensive transcriptomic analysis of prostate cancer lung metastases

Metastatic prostate cancer (mPCa) is a widespread disease with high mortality. Unraveling molecular mechanisms of disease progression is of utmost importance. The microenvironment in visceral organs and the skeletal system is of particular interest as a harbinger of metastatic spread. Therefore, we performed a comprehensive transcriptomic analysis of prostate cancer lung metastases with a special focus on differentially expressed genes attributable to the microenvironment. Digital gene expression analysis using the NanoString nCounter analysis system was performed on formalin-fixed, paraffin-embedded (FFPE) tissue from prostate cancer (PCa) lung metastases (n = 24). Data were compared to gene expression data from primary PCa and PCa bone metastases. Bioinformatic analysis was performed using several publicly available tools. In comparison to prostate cancer bone metastases, 209 genes were significantly upregulated, and 100 genes were significantly downregulated in prostate cancer lung metastases. Among the up-regulated genes, the top 10 genes with the most significant P-value were HLA-DPB1, PTPRC, ITGB7, C3, CCL21, CCL5, ITGAM, SERPINA1, MFAP4, ARAP2 and among the down-regulated genes, the top 10 genes with the most significant P-value were FOXC2, TWIST1, CDK14, CHAD, IBSP, EPN3, VIT, HAPLN1, SLC44A4, TBX1. In PCa lung metastases genes associated with immunogenic responses were upregulated while genes associated with epithelial-mesenchymal transition were down-regulated. We also showed that CXCR3/CXCL10 axis plays a significant role in prostate cancer lung metastases in comparison to bone metastases. In this study, we comprehensively explored transcriptomic alterations in PCa lung metastases in comparison to primary PCa and PCa bone metastases. In PCa lung metastases genes associated with immunogenic responses are upregulated while genes associated with epithelial-mesenchymal transition are down-regulated. This points to a more immunogenic phenotype of PCa lung metastases thus potentially making patients more susceptible to immunotherapeutic approaches.

  • Saraji, A.
  • Wulf, K.
  • Stegmann-Frehse, J.
  • Kang, D.
  • Offermann, A.
  • Jonigk, D.
  • Kuehnel, M. P.
  • Kirfel, J.
  • Perner, S.
  • Sailer, V. W.

Keywords

  • Male
  • Humans
  • *Prostatic Neoplasms/genetics/pathology
  • *Lung Neoplasms/genetics/secondary/pathology
  • *Gene Expression Profiling
  • *Gene Expression Regulation, Neoplastic
  • Transcriptome
  • Bone Neoplasms/secondary/genetics
  • Aged
  • Middle Aged
  • Tumor Microenvironment/genetics
Publication details
DOI: 10.1371/journal.pone.0306525
Journal: PLoS One
Pages: e0306525 
Number: 8
Work Type: Original
Location: BREATH
Disease Area: LC
Partner / Member: MHH
Access-Number: 39146303

DZL Engagements

chevron-down