The Gene Expression Landscape of Prostate Cancer BM Reveals Close Interaction with the Bone Microenvironment

Bone metastatic (BM) prostate cancer (PCa) belongs to the most lethal form of PCa, and therapeutic options are limited. Molecular profiling of metastases contributes to the understanding of mechanisms defining the bone metastatic niche. Our aim was to explore the transcriptional profile of PCa BM an...

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Main Authors: Alireza Saraji, Kang Duan, Christian Watermann, Katharina Hempel, Marie C. Roesch, Rosemarie Krupar, Janine Stegmann-Frehse, Danny Jonigk, Mark Philipp Kuehnel, Wolfram Klapper, Axel S. Merseburger, Jutta Kirfel, Sven Perner, Anne Offermann, Verena Sailer
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/21/13029
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author Alireza Saraji
Kang Duan
Christian Watermann
Katharina Hempel
Marie C. Roesch
Rosemarie Krupar
Janine Stegmann-Frehse
Danny Jonigk
Mark Philipp Kuehnel
Wolfram Klapper
Axel S. Merseburger
Jutta Kirfel
Sven Perner
Anne Offermann
Verena Sailer
author_facet Alireza Saraji
Kang Duan
Christian Watermann
Katharina Hempel
Marie C. Roesch
Rosemarie Krupar
Janine Stegmann-Frehse
Danny Jonigk
Mark Philipp Kuehnel
Wolfram Klapper
Axel S. Merseburger
Jutta Kirfel
Sven Perner
Anne Offermann
Verena Sailer
author_sort Alireza Saraji
collection DOAJ
description Bone metastatic (BM) prostate cancer (PCa) belongs to the most lethal form of PCa, and therapeutic options are limited. Molecular profiling of metastases contributes to the understanding of mechanisms defining the bone metastatic niche. Our aim was to explore the transcriptional profile of PCa BM and to identify genes that drive progression. Paraffin-embedded tissues of 28 primary PCa and 30 BM were submitted to RNA extraction and analyzed by RNA sequencing using the Nanostring nCounter gene expression platform. A total of 770 cancer-related genes were measured using the Nanostring™ PanCancer progression panel. Gene Ontology (GO), KEGG, Reactome, STRING, Metascape, PANTHER, and Pubmed were used for data integration and gene annotation. We identified 116 differentially expressed genes (DEG) in BM compared to primaries. The most significant DEGs include <i>CD36</i>, <i>FOXC2</i>, <i>CHAD</i>, <i>SPP1</i>, <i>MMPs</i>, <i>IBSP</i>, and <i>PTX3</i>, which are more highly expressed in BM, and <i>ACTG2</i>, <i>MYH11</i>, <i>CNN1</i>, <i>FGF2</i>, <i>SPOCK3</i>, and <i>CHRDL1</i>, which have a lower expression. DEGs functionally relate to extracellular matrix (ECM) proteoglycans, ECM-receptors, cell-substrate adhesion, cell motility as well as receptor tyrosine kinase signaling and response to growth factors. Data integration and gene annotation of 116 DEGs were used to build a gene platform which we termed “Manually Annotated and Curated Nanostring-data Platform”. In summary, our results highlight the significance of certain genes in PCa BM to which essential pro-metastatic functions could be ascribed. Data from this study provide a comprehensive platform of genes that are related to PCa BM and provide evidence for further investigations.
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spelling doaj.art-5722d2c076dd4b6783f6361a947703812023-11-24T05:01:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123211302910.3390/ijms232113029The Gene Expression Landscape of Prostate Cancer BM Reveals Close Interaction with the Bone MicroenvironmentAlireza Saraji0Kang Duan1Christian Watermann2Katharina Hempel3Marie C. Roesch4Rosemarie Krupar5Janine Stegmann-Frehse6Danny Jonigk7Mark Philipp Kuehnel8Wolfram Klapper9Axel S. Merseburger10Jutta Kirfel11Sven Perner12Anne Offermann13Verena Sailer14Institute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, GermanyInstitute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, GermanyInstitute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, GermanyInstitute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, GermanyDepartment of Urology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, GermanyResearch Center Borstel, Leibniz Lung Center, 23845 Borstel, GermanyInstitute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, GermanyInstitute of Pathology, Hannover Medical School, 30625 Hannover, GermanyInstitute of Pathology, Hannover Medical School, 30625 Hannover, GermanyInstitute of Pathology, Hematopathology Section and Lymph Node Registry, Universitätsklinikum Schleswig-Holstein, Campus Kiel, 24105 Kiel, GermanyDepartment of Urology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, GermanyInstitute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, GermanyInstitute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, GermanyInstitute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, GermanyInstitute of Pathology, University Hospital Schleswig-Holstein, Campus Luebeck, 23538 Luebeck, GermanyBone metastatic (BM) prostate cancer (PCa) belongs to the most lethal form of PCa, and therapeutic options are limited. Molecular profiling of metastases contributes to the understanding of mechanisms defining the bone metastatic niche. Our aim was to explore the transcriptional profile of PCa BM and to identify genes that drive progression. Paraffin-embedded tissues of 28 primary PCa and 30 BM were submitted to RNA extraction and analyzed by RNA sequencing using the Nanostring nCounter gene expression platform. A total of 770 cancer-related genes were measured using the Nanostring™ PanCancer progression panel. Gene Ontology (GO), KEGG, Reactome, STRING, Metascape, PANTHER, and Pubmed were used for data integration and gene annotation. We identified 116 differentially expressed genes (DEG) in BM compared to primaries. The most significant DEGs include <i>CD36</i>, <i>FOXC2</i>, <i>CHAD</i>, <i>SPP1</i>, <i>MMPs</i>, <i>IBSP</i>, and <i>PTX3</i>, which are more highly expressed in BM, and <i>ACTG2</i>, <i>MYH11</i>, <i>CNN1</i>, <i>FGF2</i>, <i>SPOCK3</i>, and <i>CHRDL1</i>, which have a lower expression. DEGs functionally relate to extracellular matrix (ECM) proteoglycans, ECM-receptors, cell-substrate adhesion, cell motility as well as receptor tyrosine kinase signaling and response to growth factors. Data integration and gene annotation of 116 DEGs were used to build a gene platform which we termed “Manually Annotated and Curated Nanostring-data Platform”. In summary, our results highlight the significance of certain genes in PCa BM to which essential pro-metastatic functions could be ascribed. Data from this study provide a comprehensive platform of genes that are related to PCa BM and provide evidence for further investigations.https://www.mdpi.com/1422-0067/23/21/13029BMprostate cancertranscriptometumor microenvironment
spellingShingle Alireza Saraji
Kang Duan
Christian Watermann
Katharina Hempel
Marie C. Roesch
Rosemarie Krupar
Janine Stegmann-Frehse
Danny Jonigk
Mark Philipp Kuehnel
Wolfram Klapper
Axel S. Merseburger
Jutta Kirfel
Sven Perner
Anne Offermann
Verena Sailer
The Gene Expression Landscape of Prostate Cancer BM Reveals Close Interaction with the Bone Microenvironment
International Journal of Molecular Sciences
BM
prostate cancer
transcriptome
tumor microenvironment
title The Gene Expression Landscape of Prostate Cancer BM Reveals Close Interaction with the Bone Microenvironment
title_full The Gene Expression Landscape of Prostate Cancer BM Reveals Close Interaction with the Bone Microenvironment
title_fullStr The Gene Expression Landscape of Prostate Cancer BM Reveals Close Interaction with the Bone Microenvironment
title_full_unstemmed The Gene Expression Landscape of Prostate Cancer BM Reveals Close Interaction with the Bone Microenvironment
title_short The Gene Expression Landscape of Prostate Cancer BM Reveals Close Interaction with the Bone Microenvironment
title_sort gene expression landscape of prostate cancer bm reveals close interaction with the bone microenvironment
topic BM
prostate cancer
transcriptome
tumor microenvironment
url https://www.mdpi.com/1422-0067/23/21/13029
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