Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of prostate cancer. Although long-noncoding RNAs (lncRNAs) have been implicated in mCRPC, past studies have relied on bulk sequencing methods with low depth and lack of single-cell resolution. Hence, we performed a lncRNA-focused analysis of single-cell RNA-sequencing data (n = 14) from mCRPC biopsies followed by integration with bulk multi-omic datasets. This yielded 389 cell-enriched lncRNAs in prostate cancer cells and the tumor microenvironment (TME). These lncRNAs demonstrated enrichment with regulatory elements and exhibited alterations during prostate cancer progression. Prostate-lncRNAs were correlated with AR mutational status and response to treatment with enzalutamide, while TME-lncRNAs were associated with RB1 deletions and poor prognosis. Finally, lncRNAs identified between prostate adenocarcinomas and neuroendocrine tumors exhibited distinct expression and methylation profiles. Our findings demonstrate the ability of single-cell analysis to refine our understanding of lncRNAs in mCRPC and serve as a resource for future mechanistic studies.
NPJ genomic medicine. 2024 Feb 23*** epublish ***
Debanjan Saha, Ha X Dang, Meng Zhang, David A Quigley, Felix Y Feng, Christopher A Maher
Medical Scientist Training Program, Washington University in St. Louis, St. Louis, MO, USA., Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO, USA., Department of Radiation Oncology, University of California at San Francisco, San Francisco, CA, USA., Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA., Department of Internal Medicine, Washington University in St. Louis, St. Louis, MO, USA. .