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Prognostic Markers in Tyrosine Kinases Specific to Basal-like 2 Subtype of Triple-Negative Breast Cancer.
International Journal of Molecular Sciences 2024 January 25
Triple-negative breast cancer (TNBC), a heterogeneous and therapeutically challenging subtype, comprises over 50% of patients categorized into basal-like 1 (BL1) and basal-like 2 (BL2) intrinsic molecular subtypes. Despite their shared basal-like classification, BL2 is associated with a poor response to neoadjuvant chemotherapy and reduced relapse-free survival compared to BL1. Here, the study focused on identifying subtype-specific markers for BL2 through transcriptomic analysis of TNBC patients using RNA-seq and clinical integration. Six receptor tyrosine kinase (TK) genes, including EGFR , EPHA4 , EPHB2 , PDGFRA , PDGFRB , and ROR1 , were identified as potential differentiators for BL2. Correlations between TK mRNA expression and TNBC prognosis, particularly EGFR , PDGFRA , and PDGFRB , revealed potential synergistic interactions in pathways related to cell survival and proliferation. Our findings also suggest promising dual markers for predicting disease prognosis. Furthermore, RT-qPCR validation demonstrated that identified BL2-specific TKs were expressed at a higher level in BL2 than in BL1 cell lines, providing insights into unique characteristics. This study advances the understanding of TNBC heterogeneity within the basal-like subtypes, which could lead to novel clinical treatment approaches and the development of targeted therapies.
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