Molecular Implications of ADIPOQ, GAS5, GATA4, and YAP1 Methylation in Triple-Negative Breast Cancer Prognosis

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Abstract
The aim of this study was to investigate the prognostic and predictive properties of four specific genes in triple-negative breast cancer (TNBC). We focused on ADIPOQ, GAS5, GATA4, and YAP1, which are known for their roles in key molecular pathways related to tumorigenesis, such as adipokine signaling, lncRNA regulation, transcriptional control, and Hippo signaling, but have not been sufficiently explored in the context of epigenetic regulation in breast cancer. Using the methylospecific PCR (MSP) method, we analyzed the methylation of the four genes in the tumor tissues collected from 57 TNBC patients. We evaluated their association with response to neoadjuvant treatment and clinicopathological characteristics. Additionally, we performed a bioinformatic analysis of methylation and expression data from The Cancer Genome Atlas (TCGA) TNBC cohort to explore their relationships with overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), progression-free interval (PFI), and relapse-free survival (RFS). No significant associations were observed between methylation patterns and clinicopathological characteristics in the patients. However, in silico analysis of the TNBC cohort identified ADIPOQ methylation as having the most significant associations, correlating with all five survival endpoints, including OS, DSS, DFI, PFI, and RFS. GAS5 methylation was significantly associated with OS, DSS, and RFS, and GATA4 methylation showed significant associations with PFI, whereas YAP1 methylation was significantly associated with OS and RFS. In addition, GAS5 expression was linked to DSS, DFI and RFS. This study highlights the potential prognostic significance of the epigenetic regulation of ADIPOQ in TNBC. The in silico findings shed light on the molecular pathways associated with TNBC progression and warrant further investigation to validate their role in clinical outcomes and underlying biological mechanisms.

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