Comprehensive transcriptomic analysis of prostate cancer lung metastases.

Autor: Saraji A; Pathology of the University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany., Wulf K; Pathology of the University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany., Stegmann-Frehse J; Pathology of the University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany., Kang D; Guangdong Second Provincial General Hospital, Guangzhou, P. R. China., Offermann A; Institute of Pathology, University of Muenster, Muenster, Germany., Jonigk D; Institute of Pathology, RWTH Aachen, Aachen, Germany., Kuehnel MP; Institute of Pathology, Hannover Medical School, Hannover, Germany.; Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research, Hannover, Germany., Kirfel J; Pathology of the University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany., Perner S; Institute for Hematopathology, Hamburg, Germany., Sailer VW; Pathology of the University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Aug 15; Vol. 19 (8), pp. e0306525. Date of Electronic Publication: 2024 Aug 15 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0306525
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Saraji et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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