Adverse prognosis gene expression patterns in metastatic castration‐resistant prostate cancer
Metastatic castration‐resistant prostate cancer (mCRPC) is a heterogeneous disease. Several studies have identified transcriptional subtypes of mCRPC, but comprehensive analysis of prognostic gene expression pathways has been limited. Therefore, we aggregated a cohort of 1012 mCRPC tissue samples fr...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Molecular Oncology |
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| Online Access: | https://doi.org/10.1002/1878-0261.70001 |
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| author | Marina N. Sharifi Eric Feng Nicholas R. Rydzewski Amy K. Taylor Jamie M. Sperger Yue Shi Kyle T. Helzer Matthew L. Bootsma Viridiana Carreno Alex H. Chang Luke A. Nunamaker Grace C. Blitzer Tianfu Andy Shang Aishwarya Subramanian Anders Bjartell Andreas Josefsson Pernilla Wikström Emily Feng Manish Kohli Rendong Yang Scott M. Dehm Eric J. Small Rahul Aggarwal David A. Quigley Joshua M. Lang Shuang G. Zhao Martin Sjöström |
| author_facet | Marina N. Sharifi Eric Feng Nicholas R. Rydzewski Amy K. Taylor Jamie M. Sperger Yue Shi Kyle T. Helzer Matthew L. Bootsma Viridiana Carreno Alex H. Chang Luke A. Nunamaker Grace C. Blitzer Tianfu Andy Shang Aishwarya Subramanian Anders Bjartell Andreas Josefsson Pernilla Wikström Emily Feng Manish Kohli Rendong Yang Scott M. Dehm Eric J. Small Rahul Aggarwal David A. Quigley Joshua M. Lang Shuang G. Zhao Martin Sjöström |
| author_sort | Marina N. Sharifi |
| collection | DOAJ |
| description | Metastatic castration‐resistant prostate cancer (mCRPC) is a heterogeneous disease. Several studies have identified transcriptional subtypes of mCRPC, but comprehensive analysis of prognostic gene expression pathways has been limited. Therefore, we aggregated a cohort of 1012 mCRPC tissue samples from 769 patients and investigated the association of gene expression‐based pathways with clinical outcomes and intrapatient and intratumor heterogeneity. Survival data were obtained for 272 patients. Pathway‐level enrichment was evaluated using gene set variation analysis. scRNA‐seq datasets from mCRPC tissue biopsies and circulating tumor cells were used to investigate heterogeneity of adverse pathways. We identified five pathway clusters: (a) Immune response/WNT/TGF‐beta signaling, (b) AR signaling/luminal signatures, (c) mTOR signaling and glycolysis, (d) cell proliferation, and (e) neuroendocrine differentiation. Proliferation, AR signaling loss, and glycolysis/mTOR signaling were independently prognostic. Adverse prognostic pathway scores decreased on treatment with AR signaling inhibitors, but not at progression, suggesting failure to permanently target these pathways. scRNA‐seq datasets from mCRPC tissue biopsies and circulating tumor cells were used to investigate heterogeneity of adverse pathways. Our results suggest loss of AR signaling, high proliferation, and a glycolytic phenotype as adverse prognostic pathways in mCRPC that could be used in conjunction with clinical factors to prognosticate for treatment decisions. |
| format | Article |
| id | doaj-art-e10d2587fc354709b165fb35b29a9b6e |
| institution | Kabale University |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-e10d2587fc354709b165fb35b29a9b6e2025-08-20T04:01:09ZengWileyMolecular Oncology1574-78911878-02612025-08-011982348236510.1002/1878-0261.70001Adverse prognosis gene expression patterns in metastatic castration‐resistant prostate cancerMarina N. Sharifi0Eric Feng1Nicholas R. Rydzewski2Amy K. Taylor3Jamie M. Sperger4Yue Shi5Kyle T. Helzer6Matthew L. Bootsma7Viridiana Carreno8Alex H. Chang9Luke A. Nunamaker10Grace C. Blitzer11Tianfu Andy Shang12Aishwarya Subramanian13Anders Bjartell14Andreas Josefsson15Pernilla Wikström16Emily Feng17Manish Kohli18Rendong Yang19Scott M. Dehm20Eric J. Small21Rahul Aggarwal22David A. Quigley23Joshua M. Lang24Shuang G. Zhao25Martin Sjöström26Carbone Cancer Center University of Wisconsin‐Madison WI USAHelen Diller Family Comprehensive Cancer Center University of California, San Francisco CA USADepartment of Human Oncology University of Wisconsin‐Madison WI USACarbone Cancer Center University of Wisconsin‐Madison WI USACarbone Cancer Center University of Wisconsin‐Madison WI USADepartment of Human Oncology University of Wisconsin‐Madison WI USADepartment of Human Oncology University of Wisconsin‐Madison WI USADepartment of Human Oncology University of Wisconsin‐Madison WI USADepartment of Medicine University of Wisconsin‐Madison WI USADepartment of Medicine University of Wisconsin‐Madison WI USACarbone Cancer Center University of Wisconsin‐Madison WI USADepartment of Human Oncology University of Wisconsin‐Madison WI USADepartment of Human Oncology University of Wisconsin‐Madison WI USAHelen Diller Family Comprehensive Cancer Center University of California, San Francisco CA USADepartment of Translational Medicine Lund University Malmö SwedenDepartment of Diagnostics and Interventions, Urology Umeå University SwedenDepartment of Medical Biosciences, Pathology Umeå University SwedenHelen Diller Family Comprehensive Cancer Center University of California, San Francisco CA USAHuntsman Cancer Institute University of Utah Salt Lake City UT USADepartment of Urology Northwestern University Feinberg School of Medicine Chicago IL USAMasonic Cancer Center University of Minnesota Minneapolis MN USAHelen Diller Family Comprehensive Cancer Center University of California, San Francisco CA USAHelen Diller Family Comprehensive Cancer Center University of California, San Francisco CA USAHelen Diller Family Comprehensive Cancer Center University of California, San Francisco CA USACarbone Cancer Center University of Wisconsin‐Madison WI USACarbone Cancer Center University of Wisconsin‐Madison WI USAHelen Diller Family Comprehensive Cancer Center University of California, San Francisco CA USAMetastatic castration‐resistant prostate cancer (mCRPC) is a heterogeneous disease. Several studies have identified transcriptional subtypes of mCRPC, but comprehensive analysis of prognostic gene expression pathways has been limited. Therefore, we aggregated a cohort of 1012 mCRPC tissue samples from 769 patients and investigated the association of gene expression‐based pathways with clinical outcomes and intrapatient and intratumor heterogeneity. Survival data were obtained for 272 patients. Pathway‐level enrichment was evaluated using gene set variation analysis. scRNA‐seq datasets from mCRPC tissue biopsies and circulating tumor cells were used to investigate heterogeneity of adverse pathways. We identified five pathway clusters: (a) Immune response/WNT/TGF‐beta signaling, (b) AR signaling/luminal signatures, (c) mTOR signaling and glycolysis, (d) cell proliferation, and (e) neuroendocrine differentiation. Proliferation, AR signaling loss, and glycolysis/mTOR signaling were independently prognostic. Adverse prognostic pathway scores decreased on treatment with AR signaling inhibitors, but not at progression, suggesting failure to permanently target these pathways. scRNA‐seq datasets from mCRPC tissue biopsies and circulating tumor cells were used to investigate heterogeneity of adverse pathways. Our results suggest loss of AR signaling, high proliferation, and a glycolytic phenotype as adverse prognostic pathways in mCRPC that could be used in conjunction with clinical factors to prognosticate for treatment decisions.https://doi.org/10.1002/1878-0261.70001biomarkergene expressionmetastatic castration‐resistant prostate cancerprecision medicineprognosis |
| spellingShingle | Marina N. Sharifi Eric Feng Nicholas R. Rydzewski Amy K. Taylor Jamie M. Sperger Yue Shi Kyle T. Helzer Matthew L. Bootsma Viridiana Carreno Alex H. Chang Luke A. Nunamaker Grace C. Blitzer Tianfu Andy Shang Aishwarya Subramanian Anders Bjartell Andreas Josefsson Pernilla Wikström Emily Feng Manish Kohli Rendong Yang Scott M. Dehm Eric J. Small Rahul Aggarwal David A. Quigley Joshua M. Lang Shuang G. Zhao Martin Sjöström Adverse prognosis gene expression patterns in metastatic castration‐resistant prostate cancer Molecular Oncology biomarker gene expression metastatic castration‐resistant prostate cancer precision medicine prognosis |
| title | Adverse prognosis gene expression patterns in metastatic castration‐resistant prostate cancer |
| title_full | Adverse prognosis gene expression patterns in metastatic castration‐resistant prostate cancer |
| title_fullStr | Adverse prognosis gene expression patterns in metastatic castration‐resistant prostate cancer |
| title_full_unstemmed | Adverse prognosis gene expression patterns in metastatic castration‐resistant prostate cancer |
| title_short | Adverse prognosis gene expression patterns in metastatic castration‐resistant prostate cancer |
| title_sort | adverse prognosis gene expression patterns in metastatic castration resistant prostate cancer |
| topic | biomarker gene expression metastatic castration‐resistant prostate cancer precision medicine prognosis |
| url | https://doi.org/10.1002/1878-0261.70001 |
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