Single cell-transcriptomic analysis informs the lncRNA landscape in metastatic castration resistant prostate cancer.
Debanjan SahaHa X DangMeng ZhangDavid A QuigleyFelix Y FengChristopher A MaherPublished in: NPJ genomic medicine (2024)
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.
Keyphrases
- single cell
- prostate cancer
- rna seq
- poor prognosis
- long non coding rna
- network analysis
- high throughput
- genome wide analysis
- radical prostatectomy
- genome wide identification
- squamous cell carcinoma
- small cell lung cancer
- neuroendocrine tumors
- transcription factor
- genome wide
- stem cells
- gene expression
- long noncoding rna
- optical coherence tomography
- mesenchymal stem cells
- single molecule
- binding protein
- cell therapy
- ultrasound guided
- combination therapy