Ribeiro Joana Martins, Mendes João, Gante Inês, Figueiredo-Dias Margarida, Almeida Vânia, Gomes Ana, Regateiro Fernando Jesus, Regateiro Frederico Soares, Caramelo Francisco, Silva Henriqueta Coimbra
Laboratory of Sequencing and Functional Genomics of UCGenomics, Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
Institute for Clinical and Biomedical Research (iCBR), Centre of Investigation on Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal.
Cancers (Basel). 2024 Aug 19;16(16):2881. doi: 10.3390/cancers16162881.
In the management of early-stage breast cancer (BC), lymph nodes (LNs) are typically characterised using the One-Step Nucleic Acid Amplification (OSNA) assay, a standard procedure for assessing subclinical metastasis in sentinel LNs (SLNs). The pivotal role of LNs in coordinating the immune response against BC is often overlooked. Our aim was to improve prognostic information provided by the OSNA assay and explore immune-related gene signatures in SLNs. The expression of an immune gene panel was analysed in SLNs from 32 patients with Luminal A early-stage BC (cT1-T2 N0). Using an unsupervised approach based on these expression values, this study identified two clusters, regardless of the SLN invasion: one evidencing an adaptive anti-tumoral immune response, characterised by an increase in naive B cells, follicular T helper cells, and activated NK cells; and another with a more undifferentiated response, with an increase in the activated-to-resting dendritic cells (DCs) ratio. Through a protein-protein interaction (PPI) network, we identified seven immunoregulatory hub genes: , , , , , , and . This study shows that, in Luminal A early-stage BC, SLNs gene expression studies enable the identification of distinct immune profiles that may influence prognosis stratification and highlight key genes that could serve as potential targets for immunotherapy.
在早期乳腺癌(BC)的管理中,淋巴结(LNs)通常使用一步核酸扩增(OSNA)检测进行特征描述,这是评估前哨淋巴结(SLNs)亚临床转移的标准程序。淋巴结在协调针对乳腺癌的免疫反应中的关键作用常常被忽视。我们的目标是改善OSNA检测提供的预后信息,并探索前哨淋巴结中的免疫相关基因特征。分析了32例 Luminal A 型早期乳腺癌(cT1-T2 N0)患者前哨淋巴结中免疫基因 panel 的表达。基于这些表达值,采用无监督方法,本研究确定了两个簇,无论前哨淋巴结是否受侵:一个表现为适应性抗肿瘤免疫反应,其特征是初始B细胞、滤泡辅助性T细胞和活化NK细胞增加;另一个反应更未分化,活化树突状细胞(DCs)与静息树突状细胞的比例增加。通过蛋白质-蛋白质相互作用(PPI)网络,我们确定了七个免疫调节枢纽基因: , , , , , ,和 。本研究表明,在 Luminal A 型早期乳腺癌中,前哨淋巴结基因表达研究能够识别可能影响预后分层的不同免疫谱,并突出可作为免疫治疗潜在靶点的关键基因。