PO.CL01.22 · 临床研究
血清蛋白质组学分析揭示三阴性乳腺癌中转移相关的分子特征及早期全身重塑
Serum proteomic profiling reveals metastasis-associated molecular signatures and early systemic remodeling in triple-negative breast cancer
该海报暂无可下载的资料
AACR 官方页面
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景与目的：三阴性乳腺癌（TNBC）是一种侵袭性亚型，远处转移风险高，且用于早期检测复发的生物标志物有限。临床监测依赖于影像学，而影像学往往仅在全身性进展后才能发现转移。本研究评估了血清蛋白质组学分析是否能识别与TNBC转移转变相关的分子变化。方法：从29例TNBC患者和10例健康供者采集血清样本。在TNBC病例中，分别有12份和9份样本在初诊时采集自从未发生远处复发的患者（NR-DIG）和发生远处复发的患者（DR-DIG）。8份样本在复发时采集（DR-REC）。所有样本均使用SomaScan® 11K蛋白质组学平台分析。进行了差异蛋白表达分析（|log₂[倍数变化]| > 0.35，错误发现率（FDR）< 0.10）、通路富集分析和免疫解卷积分析。结果：DR-REC与DR-DIG之间的比较鉴定出299种差异表达蛋白（DEPs；260种上调，39种下调）。DEPs显著富集于炎症、凝血、血管生成和细胞外基质重塑。无监督层次聚类将DR-REC与DR-DIG区分开来，其中一份临床分类为DR-DIG的血清样本与DR-REC聚为一类，提示转移相关的蛋白质组学变化可能先于临床检测。免疫解卷积显示，与NR-DIG和DR-DIG相比，DR-REC中单核细胞和中性粒细胞特征增加，表明转移进展过程中存在全身性免疫重塑。结论：血清蛋白质组学分析能够检测与TNBC转移转变相关的分子改变，甚至先于复发的影像学证据。这些发现支持基于蛋白质组学的液体活检作为一种微创方法用于TNBC转移进展的早期检测和监测的可行性。
查看英文原文 English abstract
Background and Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype with high risk of distant metastasis and limited biomarkers for early detection of recurrence. Clinical surveillance relies on imaging, which often identifies metastasis only after systemic progression. This study evaluated whether serum proteomic profiling can identify molecular changes associated with metastatic transition in TNBC. Methods: Serum samples were collected from 29 patients with TNBC and 10 healthy donors. Among TNBC cases, 12 and 9 samples were obtained at the time of initial diagnosis from patients who never developed distant recurrence (NR-DIG) and those who developed distant recurrence (DR-DIG), respectively. Eight samples were collected at recurrence (DR-REC). All samples were analyzed using the SomaScan® 11K proteomic platform. Differential protein expression (|log₂[Fold Change]| > 0.35, False Discovery Rate (FDR) < 0.10), pathway enrichment, and immune deconvolution analyses were performed. Results: Comparison between DR-REC and DR-DIG identified 299 differentially expressed proteins (DEPs; 260 upregulated, 39 downregulated). Inflammation, coagulation, angiogenesis, and extracellular matrix remodeling were significantly enriched by the DEPs. Unsupervised hierarchical clustering distinguished DR-REC from DR-DIG, and one serum sample clinically classified as DR-DIG clustered with DR-REC, suggesting that metastasis-associated proteomic changes may precede clinical detection. Immune deconvolution revealed increased monocyte and neutrophil signatures in DR-REC compared with NR-DIG and DR-DIG, indicating systemic immune remodeling during metastatic progression. Conclusions: Serum proteomic profiling can detect molecular alterations associated with metastatic transition in TNBC, even before radiographic evidence of recurrence. These findings support the feasibility of a proteomics-based liquid biopsy as a minimally invasive approach for early detection and monitoring of metastatic progression in TNBC.
利益披露 Disclosure
J. Kim, None..
H. Kim, None..
S. Tanaka, None..
T. Fujii, None..
S. You, None..
H. Furuya, None.