The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Molecular profiling stratifies diverse phenotypes of treatment-refractory metastatic castration-resistant prostate cancer
Open accessAbstract
Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease with diverse drivers of disease progression and mechanisms of therapeutic resistance. We conducted deep phenotypic characterization of CRPC metastases and patient-derived xenograft (PDX) lines using whole genome RNA sequencing, gene set enrichment analysis and immunohistochemistry. Our analyses revealed five mCRPC phenotypes based on the expression of well-characterized androgen receptor (AR) or neuroendocrine (NE) genes: (i) AR-high tumors (ARPC), (ii) AR-low tumors (ARLPC), (iii) amphicrine tumors composed of cells co-expressing AR and NE genes (AMPC), (iv) double-negative tumors (i.e. AR-/NE-; DNPC) and (v) tumors with small cell or NE gene expression without AR activity (SCNPC). RE1-silencing transcription factor (REST) activity, which suppresses NE gene expression, was lost in AMPC and SCNPC PDX models. However, knockdown of REST in cell lines revealed that attenuated REST activity drives the AMPC phenotype but is not sufficient for SCNPC conversion. We also identified a subtype of DNPC tumors with squamous differentiation and generated an encompassing 26-gene transcriptional signature that distinguished the five mCRPC phenotypes. Together, our data highlight the central role of AR and REST in classifying treatment-resistant mCRPC phenotypes. These molecular classifications could potentially guide future therapeutic studies and clinical trial design.
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Cites
GSVA: gene set variation analysis for microarray and RNA-Seq data
Hänzelmann, S., Castelo, R., & Guinney, J. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-7 · Cited by 15,440
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013) · Genome Biology · doi:10.1186/gb-2013-14-4-r36 · Cited by 12,668
GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists
Eden, E., Navon, R., Steinfeld, I., Lipson, D., & Yakhini, Z. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-48 · Cited by 3,356
Abiraterone in Metastatic Prostate Cancer without Previous Chemotherapy
Ryan, C. J., Smith, M. R., de Bono, J. S., Molina, A., Logothetis, C. J., de Souza, P., Fizazi, K., Mainwaring, P., Piulats, J. M., Ng, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1209096 · Cited by 2,796
Self-citationDevelopment of a second-generation antiandrogen for treatment of advanced prostate cancer.
Tran, C., Ouk, S., Clegg, N. J., Chen, Y., Watson, P. A., Arora, V., Wongvipat, J., Smith-Jones, P. M., Yoo, D., Kwon, A., et al. (2009) · Science · doi:10.1126/science.1168175 · Cited by 2,292
Self-citationAggarwal, R., Huang, J., Alumkal, J. J., Zhang, L., Feng, F. Y., Thomas, G. V., Weinstein, A. S., Friedl, V., Zhang, C., Witte, O. N., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.77.6880 · Cited by 810
Self-citationAndrogen Receptor Pathway-Independent Prostate Cancer Is Sustained through FGF Signaling
Bluemn, E. G., Coleman, I. M., Lucas, J. M., Coleman, R. T., Hernandez-Lopez, S., Tharakan, R., Bianchi-Frias, D., Dumpit, R. F., Kaipainen, A., Corella, A. N., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.09.003 · Cited by 744
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Cited by
FOXA2 drives lineage plasticity and KIT pathway activation in neuroendocrine prostate cancer
Han, M., Li, F., Zhang, Y., Dai, P., He, J., Li, Y., Zhu, Y., Zheng, J., Huang, H., Bai, F., et al. (2022) · Cancer Cell · doi:10.1016/j.ccell.2022.10.011 · Cited by 166
A human multi-lineage hepatic organoid model for liver fibrosis
Guan, Y., Enejder, A., Wang, M., Fang, Z., Cui, L., Chen, S.-Y., Wang, J., Tan, Y., Wu, M., Chen, X., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-26410-9 · Cited by 149
Metadata
- Authors
- Labrecque, M. P., Coleman, I. M., Brown, L. G., True, L. D., Kollath, L., Lakely, B., Nguyen, H. M., Yang, Y. C., da Costa, R. M. G., Kaipainen, A., Coleman, R., Higano, C. S., Yu, E. Y., Cheng, H. H., Mostaghel, E. A., Montgomery, B., Schweizer, M. T., Hsieh, A. C., Lin, D. W., Corey, E., Nelson, P. S., & Morrissey, C.
- Venue
- Journal of Clinical Investigation
- Published
- 2019-09-16
- Volume
- 129
- Issue
- 10
- Pages
- 4492-4505
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2965156742
- Cited by
- 464
- References
- 7
- FWCI
- 25.86
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
