Clinical value of molecular subtypes identification based on anoikis-related lncRNAs in castration-resistant prostate...

Area of Science:

• Oncology
• Molecular Biology
• Bioinformatics

Background:

• Anoikis, a form of programmed cell death, plays a role in tumor progression and metastasis.
• The specific function of anoikis in castration-resistant prostate cancer (CRPC) is not well understood.
• This study investigates the role of anoikis-related long non-coding RNAs (arlncRNAs) in CRPC.

Purpose of the Study:

• To develop a prognostic indicator for CRPC based on arlncRNAs.
• To explore the biological functions of arlncRNAs in CRPC.
• To identify potential therapeutic targets and drug sensitivities in CRPC.

Main Methods:

• Differential gene expression analysis of anoikis-related genes in CRPC datasets (GSE51873, GSE78201).
• Selection and risk model development using four prognostic arlncRNAs, validated in TCGA and MSKCC cohorts.
• Functional analyses including KEGG enrichment, immune infiltration, immune checkpoint expression, drug susceptibility, CCK-8 assays, colony formation assays, and flow cytometry.

Main Results:

• A prognostic index (ARPI) based on four arlncRNAs was developed and validated, classifying CRPC patients into two subtypes.
• High-ARPI group was associated with enriched cancer and immune-related pathways and increased immune infiltration.
• Specific drugs (Fulvestrant, OSI-027, Lapatinib, Dabrafenib, Palbociclib) showed potential sensitivity in high-ARPI patients.
• Silencing LINC01138 inhibited proliferation, migration, and enzalutamide resistance, while promoting apoptosis and inhibiting epithelial-mesenchymal transition in CRPC.

Conclusions:

• Four arlncRNAs were identified, forming a risk model to predict prostate cancer prognosis.
• Immune infiltration and drug susceptibility analyses suggest potential therapeutic strategies for CRPC patients.