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Published on: September 19, 2018
Transcriptomic Analysis of Subtype-Specific Tyrosine Kinases as Triple Negative Breast Cancer Biomarkers
Praopim Limsakul1,2, Pongsakorn Choochuen3, Gorn Charupanit4,5
1Division of Physical Science, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand.
Abstract:
Triple negative breast cancer (TNBC) shows impediment to the development of targeted therapies due to the absence of specific molecular targets. The high heterogeneity across TNBC subtypes, which can be classified to be at least four subtypes, including two basal-like (BL1, BL2), a mesenchymal (M), and a luminal androgen receptor (LAR) subtype, limits the response to cancer therapies. Despite many attempts to identify TNBC biomarkers, there are currently no effective targeted therapies against this malignancy. In this study, thus, we identified the potential tyrosine kinase (TK) genes that are uniquely expressed in each TNBC subtype, since TKs have been typically used as drug targets. Differentially expressed TK genes were analyzed from The Cancer Genome Atlas (TCGA) database and were confirmed with the other datasets of both TNBC patients and cell lines. The results revealed that each TNBC subtype expressed distinct TK genes that were specific to the TNBC subtype. The identified subtype-specific TK genes of BL1, BL2, M, and LAR are LYN, CSF1R, FGRF2, and SRMS, respectively. These findings could serve as a potential biomarker of specific TNBC subtypes, which could lead to an effective treatment for TNBC patients.
Insights
Triple negative breast cancer (TNBC) lacks targeted therapies. This study identifies unique tyrosine kinase (TK) genes for each TNBC subtype, offering potential biomarkers for personalized treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Triple negative breast cancer (TNBC) presents a therapeutic challenge due to its heterogeneity and lack of specific molecular targets.
- Current treatment strategies for TNBC are limited, with no effective targeted therapies available despite extensive biomarker research.
- TNBC is broadly classified into at least four subtypes: basal-like 1 (BL1), basal-like 2 (BL2), mesenchymal (M), and luminal androgen receptor (LAR).
Purpose of the Study:
- To identify potential tyrosine kinase (TK) genes that are uniquely expressed in each distinct TNBC subtype.
- To explore TK genes as potential therapeutic targets given their established role in cancer drug development.
- To discover subtype-specific biomarkers for improved TNBC treatment strategies.
Main Methods:
- Analysis of differentially expressed TK genes using The Cancer Genome Atlas (TCGA) database.
- Validation of identified TK genes using additional datasets from TNBC patients and cell lines.
- Bioinformatic analysis to pinpoint TK genes specific to BL1, BL2, M, and LAR TNBC subtypes.
Main Results:
- Each TNBC subtype exhibits a distinct set of expressed TK genes.
- The study identified subtype-specific TK genes: LYN for BL1, CSF1R for BL2, FGRF2 for M, and SRMS for LAR.
- These identified TK genes represent potential biomarkers for classifying TNBC subtypes.
Conclusions:
- The identified TK genes are specific to individual TNBC subtypes, highlighting molecular differences.
- These subtype-specific TK genes hold promise as biomarkers for targeted therapy development in TNBC.
- This research could pave the way for more effective and personalized treatment approaches for TNBC patients.
