Bam Amjila, Hu Yawen, Wu Xiaocheng, Luo Meng, Rizvi Nubaira, Del Valle Luis, Zea Arnold H, Hossain Fokhrul, Danos Denise Moore, Zabaleta Jovanny, Ochoa Augusto, Miele Lucio, Trapido Edward, Yu Qingzhao
School of Public Health, LSU-Health Sciences Center, New Orleans, LA 70112, USA.
School of Medicine, LSU-Health Sciences Center, New Orleans, LA 70112, USA.
Cancers (Basel). 2025 Aug 11;17(16):2618. doi: 10.3390/cancers17162618.
Triple negative breast cancer (TNBC) is an aggressive, molecularly heterogeneous subtype of breast cancer, accounting for approximately 10-15% of all cases. While reproductive and metabolic factors contribute to breast cancer development, growing concerns about environmental exposures, alongside biological and socio-cultural influences, underscore the need for targeted prevention strategies across diverse populations. Despite increasing evidence linking biological, socioeconomic, and environmental factors to TNBC outcomes, the molecular mechanisms underlying these relationships remain poorly understood. Micro-RNAs (miRNAs), which regulate gene expression and play critical roles in cancer development, have emerged as potential mediators between environmental exposures and TNBC progression. The goal of this research is to identify environmental risk factors that directly relate to TNBC stages and enhance understanding of the mechanisms underlying how miRNAs link environmental exposures to TNBC stages. In this study, we analyzed 434 Formalin-Fixed, Paraffin-Embedded (FFPE) tumor samples from 434 women diagnosed with TNBC between 2009 and 2019, encompassing diverse cancer stages (184 cases from early stage and 250 cases from advanced stage), racial backgrounds, and socioeconomic statuses. The sequencing data were linked with the Louisiana Tumor Registry data and the Environmental Justice index. A total of 348 unique miRNAs were identified as differentially expressed across environmental risk factors statistically associated with TNBC stage, adjusting for plate effects. An UpSet plot revealed 44 miRNAs commonly differentially expressed across TNBC stages and multiple environmental exposures. At least one differentially expressed (DE) miRNA was shared between the TNBC stage and each environmental factor, with many associated with receptor-negative and aggressive breast cancer subtypes. These findings highlight potential biological pathways through which exposures may drive the TNBC progression and contribute to disparities in outcomes.
三阴性乳腺癌（TNBC）是一种侵袭性、分子异质性的乳腺癌亚型，约占所有病例的10%-15%。虽然生殖和代谢因素会促使乳腺癌的发生，但人们对环境暴露以及生物和社会文化影响的日益关注，凸显了针对不同人群制定有针对性预防策略的必要性。尽管越来越多的证据表明生物、社会经济和环境因素与TNBC的预后相关，但这些关系背后的分子机制仍知之甚少。微小RNA（miRNA）可调节基因表达并在癌症发展中起关键作用，已成为环境暴露与TNBC进展之间的潜在介质。本研究的目的是确定与TNBC分期直接相关的环境风险因素，并加深对miRNA将环境暴露与TNBC分期联系起来的潜在机制的理解。在本研究中，我们分析了2009年至2019年间被诊断为TNBC的434名女性的434份福尔马林固定、石蜡包埋（FFPE）肿瘤样本，这些样本涵盖了不同的癌症分期（早期184例，晚期250例）、种族背景和社会经济状况。测序数据与路易斯安那肿瘤登记数据和环境正义指数相关联。在调整板效应后，共鉴定出348种独特的miRNA在与TNBC分期有统计学关联的环境风险因素中差异表达。一个UpSet图显示，有44种miRNA在TNBC分期和多种环境暴露中普遍差异表达。TNBC分期与每个环境因素之间至少共享一种差异表达（DE）miRNA，其中许多与受体阴性和侵袭性乳腺癌亚型相关。这些发现突出了暴露可能推动TNBC进展并导致预后差异的潜在生物学途径。
