Differentially Expressed Genes in Multifocal and Multicentric Breast Cancer (MMBC) and Their Role in Breast Cancer Progression: A Multi-Cohort Analysis

Differentially Expressed Genes in Multifocal and Multicentric Breast Cancer (MMBC) and Their Role in Breast Cancer Progression: A Multi-Cohort Analysis

Presenter(s)

Thanh Chu

Comments

3:00-4:15, Kennedy Union Ballroom

Description

Breast cancer has been considered as the second contributor to cancer-related fatalities among women worldwide. Among different categories of breast tumors, multifocal and multicentric breast cancers (MMBC) tend to be more aggressive than unifocal tumors and are highly associated with lower survival rates, higher recurrence rates, and increased lymph node metastasis. Despite its clinical significance, the underlying mechanisms governing MMBC progression have remained unclear. In this study, we utilized the advances of bioinformatics to discover key differentially expressed gens (DEGs) and associated functional pathways driving MMBC progression. Initially, we accessed and analyzed a published MMBC dataset (GSE79058) from a study of multifocal invasive lobular carcinoma (ILC) to discover DEGs clusters based on tumor grades (ILC1 and ILC2), following by enrichment analysis to reveal potentially related functional processes involved in MMBC. A total of 153 DEGs were identified in ILC1 and 265 DEGS in ILC2. Functional pathway analysis revealed several closely related pathways that could be highly impacted by MMBC. Specifically, the PI3K-AKT signaling pathway exhibits differential expression across both grades, manifesting in both up-regulated and down-regulated gene clusters. This suggests a complex interplay of genes associated with this pathway, both upstream and downstream orientation.To further discover key features of MMBC, we examined MMBC-related gene signatures across large datasets including METBRIC and SCAN-B breast cancer cohorts. Clustering analysis revealed a clear distinction between MMBC from non-MMBC cases, with HER2, Luminal A and Luminal B breast cancer subtypes exhibiting significantly higher MMBC-associated scores than normal-like subtypes. In addition, survival analysis demonstrated that MMBC patients experienced significant worse overall survival (OS) and recurrence-free survival (RFS), possibly indicating poorer prognosis. These findings shed the light for initial understandings of MMBC characteristics, by identifying and validate novel gene signatures and their functional role in tumor progression. As MMBC continues to be a significant clinical challenge, further research into its molecular drivers will be essential for developing more effective interventions aimed at improving patient outcomes.

Publication Date

4-23-2025

Project Designation

Graduate Research

Primary Advisor

Loan T. Bui

Primary Advisor's Department

Biology

Keywords

Stander Symposium, College of Arts and Sciences

Differentially Expressed Genes in Multifocal and Multicentric Breast Cancer (MMBC) and Their Role in Breast Cancer Progression: A Multi-Cohort Analysis

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