Impact of transportation infrastructure on differentially expressed miRNAs in triple negative breast cancer stages at diagnosis

Purpose: Triple negative breast cancer (TNBC) is a subtype of breast cancer (BC) characterized by the absence of estrogen, progesterone, and HER2 receptors, accounts for 10-15% of all BC cases, and is associated with poor clinical outcomes. Environmental factors such as residential proximity to major transportation infrastructure may influnce disease severity, yet evidence and molecular mechanism remain fragmented. MicroRNAs (miRNAs) regulate tumor growth and treatment response, acting as either tumor suppressors or oncogenes. Here, we investigated miRNA expression across varying environmental exposure groups in TNBC, aiming to evaluate the impact of proximity to high volumes of transportation infrastructure on clinical outcomes in TNBC patients. Methods: Total 434 TNBC patients diagnosed between 2009 and 2019 in Louisiana were included. Clinical and environmental data were integrated from Louisiana Tumor Registry (LTR) and Environmental Justice Index (EJI). RPL_EBM_DOM4 is the environmental variable representing the percentile rank of domain consisting of proximity to high volume roads, railways, and airports, and is categorized into 4 groups. TNBC stages were categorized as early or advanced. All of their Formalin-Fixed, Paraffin-Embedded (FFPE) TNBC tumor specimens were collected. MiRNA expression was profiled using high-throughput sequencing and normalized via the TMM method. Differentially expressed (DE) miRNAs were identified using edgeR, adjusting for plate effects. Shared DE miRNAs across TNBC stage and RPL_EBM_DOM4 were visualized using a Venn Diagram. All the analysis were performed using R.4.5.0. Statistical significance was considered as p<0.05.  Results: Advanced TNBC patients resided closer to major transportation infrastructure. There was a statistically significant association between RPL_EBM_DOM4 and TNBC stages (p=0.005657), indicating that environmental exposure to transportation infrastructure may increase the risk of advanced TNBC. A total of 196 miRNAs were identified as differentially expressed in relation to proximity to high-volume transportation infrastructure, and 69 miRNAs were associated with TNBC stage. Of these, 32 miRNAs were commonly differentially expressed across both RPL_EBM_DOM4 and TNBC stage. Conclusion: Our study identified miRNAs potentially mediating the influence of environmental exposures on TNBC progression. The discovery of shared DE miRNAs offers insights into the molecular mechanisms underlying TNBC and suggests potential targets for intervention and prevention strategies tailored to environmentally influenced cancer outcomes. Futher studies by incorporating additional TNBC-related outcomes (such as patient survival) and other environmental risk factors may gain more comprehensive understanding of TNBC and provide strategies for equitable healthcare.