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Updated: Mar 24, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Comprehensive transcriptome analysis identifies novel molecular subtypes and subtype-specific RNAs of triple-negative
Yi-Rong Liu1,2,3, Yi-Zhou Jiang1,2,3, Xiao-En Xu1,2,3
1Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong-An Road, Shanghai, 200032, P.R. China.
Background:
Triple-negative breast cancer (TNBC) is a highly heterogeneous group of cancers, and molecular subtyping is necessary to better identify molecular-based therapies. While some classifiers have been established, no one has integrated the expression profiles of long noncoding RNAs (lncRNAs) into such subtyping criterions. Considering the emerging important role of lncRNAs in cellular processes, a novel classification integrating transcriptome profiles of both messenger RNA (mRNA) and lncRNA would help us better understand the heterogeneity of TNBC.
Methods:
Using human transcriptome microarrays, we analyzed the transcriptome profiles of 165 TNBC samples. We used k-means clustering and empirical cumulative distribution function to determine optimal number of TNBC subtypes. Gene Ontology (GO) and pathway analyses were applied to determine the main function of the subtype-specific genes and pathways. We conducted co-expression network analyses to identify interactions between mRNAs and lncRNAs.
Results:
All of the 165 TNBC tumors were classified into four distinct clusters, including an immunomodulatory subtype (IM), a luminal androgen receptor subtype (LAR), a mesenchymal-like subtype (MES) and a basal-like and immune suppressed (BLIS) subtype. The IM subtype had high expressions of immune cell signaling and cytokine signaling genes. The LAR subtype was characterized by androgen receptor signaling. The MES subtype was enriched with growth factor signaling pathways. The BLIS subtype was characterized by down-regulation of immune response genes, activation of cell cycle, and DNA repair. Patients in this subtype experienced worse recurrence-free survival than others (log rank test, P = 0.045). Subtype-specific lncRNAs were identified, and their possible biological functions were predicted using co-expression network analyses.
Conclusions:
We developed a novel TNBC classification system integrating the expression profiles of both mRNAs and lncRNAs and determined subtype-specific lncRNAs that are potential biomarkers and targets. If further validated in a larger population, our novel classification system could facilitate patient counseling and individualize treatment of TNBC.
Insights
Researchers classified triple-negative breast cancer (TNBC) into four subtypes using messenger RNA (mRNA) and long noncoding RNA (lncRNA) expression. This novel classification identifies subtype-specific lncRNAs for potential targeted therapies in TNBC.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) is a heterogeneous cancer requiring molecular subtyping for targeted therapies.
- Current TNBC classifiers lack integration of long noncoding RNA (lncRNA) expression profiles.
- lncRNAs play crucial roles in cellular processes, necessitating their inclusion for a comprehensive TNBC understanding.
Purpose of the Study:
- To develop a novel TNBC classification system integrating both mRNA and lncRNA expression profiles.
- To identify and characterize distinct molecular subtypes within TNBC.
- To discover subtype-specific lncRNAs as potential biomarkers and therapeutic targets.
Main Methods:
- Transcriptome-wide analysis of 165 TNBC samples using microarrays.
- K-means clustering and empirical cumulative distribution function for optimal subtype determination.
- Gene Ontology, pathway, and co-expression network analyses to identify functions and interactions.
Main Results:
- Four TNBC subtypes were identified: immunomodulatory (IM), luminal androgen receptor (LAR), mesenchymal-like (MES), and basal-like and immune suppressed (BLIS).
- Each subtype exhibited distinct gene expression patterns related to immune signaling, androgen receptor, growth factors, or cell cycle/DNA repair.
- The BLIS subtype showed significantly worse recurrence-free survival.
- Subtype-specific lncRNAs were identified and their functions predicted.
Conclusions:
- A novel TNBC classification integrating mRNA and lncRNA expression was developed.
- Subtype-specific lncRNAs were identified as potential biomarkers and therapeutic targets for TNBC.
- This classification system may aid in personalized treatment strategies for TNBC patients upon further validation.
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