Background/Objectives: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.Methods: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.Results: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.Conclusions:These findings highlight potential biological pathways through which exposures may drive the TNBC progression and contribute to disparities in outcomes.
背景/目的：三阴性乳腺癌是一种具有侵袭性且分子异质性的乳腺癌亚型，约占所有乳腺癌病例的10-15%。虽然生殖和代谢因素在乳腺癌发生发展中起作用，但日益受到关注的环境暴露以及生物和社会文化影响，凸显了针对不同人群制定靶向预防策略的必要性。尽管越来越多的证据表明生物、社会经济和环境因素与三阴性乳腺癌的预后相关，但这些关联背后的分子机制仍知之甚少。微小RNA作为调控基因表达并在癌症发展中起关键作用的分子，已成为连接环境暴露与三阴性乳腺癌进展的潜在介质。本研究旨在识别与三阴性乳腺癌分期直接相关的环境风险因素，并深入理解微小RNA如何介导环境暴露影响三阴性乳腺癌分期的机制。 方法：本研究分析了2009年至2019年间434例确诊为三阴性乳腺癌的女性患者的434份福尔马林固定石蜡包埋肿瘤样本，涵盖不同癌症分期（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州肿瘤登记数据及环境公平指数进行了关联分析。 结果：在校正检测板效应后，共鉴定出348个独特的微小RNA在统计学上与三阴性乳腺癌分期相关的环境风险因素中存在差异表达。UpSet图显示44个微小RNA在三阴性乳腺癌不同分期及多种环境暴露中普遍存在差异表达。每个环境因素与三阴性乳腺癌分期之间至少共享一个差异表达的微小RNA，其中许多与受体阴性及侵袭性乳腺癌亚型相关。 结论：这些发现揭示了环境暴露可能驱动三阴性乳腺癌进展并导致预后差异的潜在生物学通路。
肿瘤(癌症)患者之家