Consensus Analysis of Whole Transcriptome Profiles from Two Breast Cancer Patient Cohorts Reveals Long Non-Coding...

Area of Science:

• Genomics
• Molecular Biology
• Cancer Research

Background:

• Long non-coding RNAs (lncRNAs) are key regulators in cellular processes and diseases like cancer.
• lncRNA expression is often specific to tumor subtypes, including breast cancer, differentiating by hormone status and molecular intrinsic subtype.
• Reproducibility of lncRNA signatures across different datasets needs further investigation.

Purpose of the Study:

• To derive consensus lncRNA signatures for breast cancer subtypes using multiple datasets.
• To identify robust lncRNA markers for specific breast cancer subtypes, particularly basal-like.
• To investigate the impact of tumor microenvironment components on lncRNA signature derivation.

Main Methods:

• Integration of differential expression analysis and hypothesis-free clustering on two clinical RNA-Seq datasets (Utah Breast Cancer Study and The Cancer Genome Atlas).
• In silico functional characterization of identified lncRNA signatures.
• Analysis of expression data from pre-clinical cancer models.

Main Results:

• A consistent lncRNA signature associated with basal-like breast cancer was identified.
• A set of six potential lncRNA markers for basal-like breast cancer was generated, with two possibly regulating known poor prognosis markers.
• Discordance in signatures across cohorts was linked to the influence of non-cancerous cells, identifying nine lncRNAs potentially associated with cancer-associated fibroblasts or immune responses.

Conclusions:

• Tumor purity significantly confounds lncRNA signature derivation in breast cancer.
• Novel hypotheses regarding the roles of lncRNAs in basal-like breast cancer and the tumor microenvironment were generated.
• This study provides a foundation for understanding lncRNA functions in breast cancer subtypes and their interactions within the tumor microenvironment.