Transcriptome Analysis Identifies Tumor Immune Microenvironment Signaling Networks Supporting Metastatic Castration-Resistant Prostate Cancer
Prostate cancer (PCa) is the second most common cause of cancer death in American men. Metastatic castration-resistant prostate cancer (mCRPC) is the most lethal form of PCa and preferentially metastasizes to the bones through incompletely understood molecular mechanisms. Herein, we processed RNA se...
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MDPI AG
2023-04-01
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| Online Access: | https://www.mdpi.com/2673-7523/3/2/7 |
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| author | Lawrence P. McKinney Rajesh Singh I. King Jordan Sooryanarayana Varambally Eric B. Dammer James W. Lillard |
| author_facet | Lawrence P. McKinney Rajesh Singh I. King Jordan Sooryanarayana Varambally Eric B. Dammer James W. Lillard |
| author_sort | Lawrence P. McKinney |
| collection | DOAJ |
| description | Prostate cancer (PCa) is the second most common cause of cancer death in American men. Metastatic castration-resistant prostate cancer (mCRPC) is the most lethal form of PCa and preferentially metastasizes to the bones through incompletely understood molecular mechanisms. Herein, we processed RNA sequencing data from patients with mCRPC (<i>n</i> = 60) and identified 14 gene clusters (modules) highly correlated with mCRPC bone metastasis. We used a novel combination of weighted gene co-expression network analysis (WGCNA) and upstream regulator and gene ontology analyses of clinically annotated transcriptomes to identify the genes. The cyan module (M14) had the strongest positive correlation (0.81, <i>p</i> = 4 × 10<sup>−15</sup>) with mCRPC bone metastasis. It was associated with two significant biological pathways through KEGG enrichment analysis (parathyroid hormone synthesis, secretion, and action and protein digestion and absorption). In particular, we identified 10 hub genes (<i>ALPL</i>, <i>PHEX</i>, <i>RUNX2</i>, <i>ENPP1</i>, <i>PHOSPHO1</i>, <i>PTH1R</i>, <i>COL11A1</i>, <i>COL24A1</i>, <i>COL22A1</i>, and <i>COL13A1</i>) using cytoHubba of Cytoscape. We also found high gene expression for collagen formation, degradation, absorption, cell-signaling peptides, and bone regulation processes through Gene Ontology (GO) enrichment analysis. |
| first_indexed | 2024-03-11T02:04:40Z |
| format | Article |
| id | doaj.art-cd65680bc0774ea68654fed2b027b775 |
| institution | Directory Open Access Journal |
| issn | 2673-7523 |
| language | English |
| last_indexed | 2024-03-11T02:04:40Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Onco |
| spelling | doaj.art-cd65680bc0774ea68654fed2b027b7752023-11-18T11:58:19ZengMDPI AGOnco2673-75232023-04-0132819510.3390/onco3020007Transcriptome Analysis Identifies Tumor Immune Microenvironment Signaling Networks Supporting Metastatic Castration-Resistant Prostate CancerLawrence P. McKinney0Rajesh Singh1I. King Jordan2Sooryanarayana Varambally3Eric B. Dammer4James W. Lillard5Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USADepartment of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USASchool of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USADivision of Molecular and Cellular Pathology, Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL 35233, USADepartment of Biochemistry Emory, University School of Medicine, Atlanta, GA 30329, USADepartment of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USAProstate cancer (PCa) is the second most common cause of cancer death in American men. Metastatic castration-resistant prostate cancer (mCRPC) is the most lethal form of PCa and preferentially metastasizes to the bones through incompletely understood molecular mechanisms. Herein, we processed RNA sequencing data from patients with mCRPC (<i>n</i> = 60) and identified 14 gene clusters (modules) highly correlated with mCRPC bone metastasis. We used a novel combination of weighted gene co-expression network analysis (WGCNA) and upstream regulator and gene ontology analyses of clinically annotated transcriptomes to identify the genes. The cyan module (M14) had the strongest positive correlation (0.81, <i>p</i> = 4 × 10<sup>−15</sup>) with mCRPC bone metastasis. It was associated with two significant biological pathways through KEGG enrichment analysis (parathyroid hormone synthesis, secretion, and action and protein digestion and absorption). In particular, we identified 10 hub genes (<i>ALPL</i>, <i>PHEX</i>, <i>RUNX2</i>, <i>ENPP1</i>, <i>PHOSPHO1</i>, <i>PTH1R</i>, <i>COL11A1</i>, <i>COL24A1</i>, <i>COL22A1</i>, and <i>COL13A1</i>) using cytoHubba of Cytoscape. We also found high gene expression for collagen formation, degradation, absorption, cell-signaling peptides, and bone regulation processes through Gene Ontology (GO) enrichment analysis.https://www.mdpi.com/2673-7523/3/2/7transcriptomicsmetastasistumor microenvironmentprostate cancersignaling |
| spellingShingle | Lawrence P. McKinney Rajesh Singh I. King Jordan Sooryanarayana Varambally Eric B. Dammer James W. Lillard Transcriptome Analysis Identifies Tumor Immune Microenvironment Signaling Networks Supporting Metastatic Castration-Resistant Prostate Cancer Onco transcriptomics metastasis tumor microenvironment prostate cancer signaling |
| title | Transcriptome Analysis Identifies Tumor Immune Microenvironment Signaling Networks Supporting Metastatic Castration-Resistant Prostate Cancer |
| title_full | Transcriptome Analysis Identifies Tumor Immune Microenvironment Signaling Networks Supporting Metastatic Castration-Resistant Prostate Cancer |
| title_fullStr | Transcriptome Analysis Identifies Tumor Immune Microenvironment Signaling Networks Supporting Metastatic Castration-Resistant Prostate Cancer |
| title_full_unstemmed | Transcriptome Analysis Identifies Tumor Immune Microenvironment Signaling Networks Supporting Metastatic Castration-Resistant Prostate Cancer |
| title_short | Transcriptome Analysis Identifies Tumor Immune Microenvironment Signaling Networks Supporting Metastatic Castration-Resistant Prostate Cancer |
| title_sort | transcriptome analysis identifies tumor immune microenvironment signaling networks supporting metastatic castration resistant prostate cancer |
| topic | transcriptomics metastasis tumor microenvironment prostate cancer signaling |
| url | https://www.mdpi.com/2673-7523/3/2/7 |
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