Single cell-transcriptomic analysis informs the lncRNA landscape in metastatic castration resistant prostate cancer

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Metastatic castration-resistant prostate cancer (mCRPC) is an aggressive malignancy with limited treatment options.
• Long-noncoding RNAs (lncRNAs) play roles in cancer, but their function in mCRPC remains unclear due to limitations of previous bulk sequencing studies.
• Single-cell resolution is needed to fully understand lncRNA heterogeneity in mCRPC.

Purpose of the Study:

• To identify and characterize cell-specific lncRNAs in mCRPC using single-cell RNA sequencing.
• To investigate the association of these lncRNAs with prostate cancer progression, tumor microenvironment (TME), and treatment response.
• To compare lncRNA profiles between prostate adenocarcinomas and neuroendocrine tumors.

Main Methods:

• Performed lncRNA-focused analysis on single-cell RNA sequencing data from 14 mCRPC biopsies.
• Integrated single-cell data with bulk multi-omic datasets.
• Analyzed lncRNA expression, correlation with genomic alterations (AR mutations, RB1 deletions), and methylation profiles.

Main Results:

• Identified 389 cell-enriched lncRNAs in prostate cancer cells and the TME.
• Discovered lncRNAs associated with regulatory elements and altered during cancer progression.
• Found prostate-lncRNAs correlated with androgen receptor (AR) mutational status and enzalutamide response.
• Linked TME-lncRNAs to RB1 deletions and poor prognosis.
• Observed distinct expression and methylation profiles for lncRNAs differentiating adenocarcinomas and neuroendocrine tumors.

Conclusions:

• Single-cell analysis provides a refined understanding of lncRNA roles in mCRPC.
• Identified lncRNAs serve as potential biomarkers for prognosis and treatment response.
• This study offers a valuable resource for future mechanistic investigations into lncRNAs in prostate cancer.