肿瘤复发和转移进展仍然是乳腺癌相关死亡的主要原因。然而，由于缺乏临床注释的纵向样本，患者匹配的原发性乳腺癌（BC）和转移性病变的蛋白质组尚未确定。在这项研究中，我们评估了有或没有远处转移的 BC 患者的整体蛋白质组图谱，并将同一患者内远处转移性疾病的蛋白质组与其相应的原发性 BC 进行了比较。我们对 73 例患者进行了基于质谱的蛋白质组分析。来自 51 名 BC 患者的血清样本。在 51 名 BC 患者中，29 名保持无转移（以下称为非进展者），22 名出现转移（以下称为进展者）。对于这 22 名进展者，我们获得了两个样本：一个在诊断后一年内收集，另一个在转移性疾病诊断前一年内收集。使用基于强度的绝对定量分析 MS 数据，并在差异表达分析之前进行归一化。对显着差异表达的蛋白质（DEP；绝对倍数变化 ≥ 1.5，P值 < 0.05，每个临床组丰度为30%）进行路径分析。我们在 BC 患者的 73 份血清样本中鉴定了 967 种蛋白质。其中，诊断时血清样本中有 39 种蛋白质在进展者和非进展者之间发生了改变。其中，当进展者发生远处转移时，有 4 种蛋白质进一步改变。此外，在进展者中，与转移开始时相比，诊断时收集的血清中有 20 种蛋白质发生了改变。通路分析表明，这些蛋白质编码描述转移的通路，包括上皮-间质转化和粘着斑，这是转移级联的标志。我们的结果强调了检查来自远处转移的匹配样本与诊断时收集的原发性 BC 样本的重要性，以揭示子集血清中可能参与 BC 进展的蛋白质。这项研究为未来的其他研究奠定了基础，这些研究可以将这些蛋白质定位为临床监测患者乳腺癌进展的非侵入性标记物。© 2024。作者。

Tumor recurrence and metastatic progression remains the leading cause for breast cancer related mortalities. However, the proteomes of patient- matched primary breast cancer (BC) and metastatic lesions have not yet been identified, due to the lack of clinically annotated longitudinal samples. In this study, we evaluated the global-proteomic landscape of BC patients with and without distant metastasis as well as compared the proteome of distant metastatic disease with its corresponding primary BC, within the same patient.We performed mass spectrometry-based proteome profiling of 73 serum samples from 51 BC patients. Among the 51 patients with BC, 29 remained metastasis-free (henceforth called non-progressors), and 22 developed metastases (henceforth called progressors). For the 22 progressors, we obtained two samples: one collected within a year of diagnosis, and the other collected within a year before the diagnosis of metastatic disease. MS data were analyzed using intensity-based absolute quantification and normalized before differential expression analysis. Significantly differentially expressed proteins (DEPs; absolute fold-change ≥ 1.5, P-value < 0.05 and 30% abundance per clinical group) were subjected to pathway analyses.We identified 967 proteins among 73 serum samples from patients with BC. Among these, 39 proteins were altered in serum samples at diagnosis, between progressors and non-progressors. Among these, 4 proteins were further altered when the progressors developed distant metastasis. In addition, within progressors, 20 proteins were altered in serum collected at diagnosis versus at the onset of metastasis. Pathway analysis showed that these proteins encoded pathways that describe metastasis, including epithelial-mesenchymal transition and focal adhesion that are hallmarks of metastatic cascade.Our results highlight the importance of examining matched samples from distant metastasis with primary BC samples collected at diagnosis to unravel subset of proteins that could be involved in BC progression in serum. This study sets the foundation for additional future investigations that could position these proteins as non-invasive markers for clinically monitoring breast cancer progression in patients.© 2024. The Author(s).